Surgical results for anterior choroidal artery (AChA) aneurysms have previously been reported as unsatisfactory due to inadvertent occlusion of the AChA, while the low incidence of AChA aneurysms hampers the accumulation of surgical experience. The authors reviewed their related surgical experience to document the ischemic complications and surgical outcomes.
Identification of the AChA at its origin by rigorous visual scrutiny, careful microdissection, and meticulous clip placement to avoid the AChA origin are all crucial surgical maneuvers. A retrospective review of a surgical series of 62 consecutive cases of an AChA aneurysm between 2004 and 2012 was performed.
All patients, except for five (8.1%) with a small residual neck, showed complete aneurysm obliteration in postoperative angiographic evaluations. There was no incidence of procedure-related permanent AChA syndrome or oculomotor nerve palsy, while three (4.8%) patients suffered from transient AChA syndrome. The clinical outcomes [the 3-month modified Rankin Scale (mRS)] of the patients were related to their preoperative World Federation of Neurologic Surgeons (WFNS) grade. As regards the 3-month mRS, significant differences were found between patients with an unruptured aneurysm (WFNS grade 0; n=20), good-grade subarachnoid hemorrhage (WFNS grade 1-3; n=30), and poor-grade subarachnoid hemorrhage (WFNS grade 4-5; n=4).
In surgical treatment of AChA aneurysms, a risk of AChA insufficiency can be minimized by taking every precaution to preserve the AChA patency and intraoperative monitoring. In addition, the surgical outcome is primarily determined by the preoperative clinical state.
Anterior choroidal artery; Anterior choroidal artery infarction; Intracranial aneurysm; Surgical procedures; Treatment outcome
In spite of the best medical treatment, large hemispheric infarction, resulting from acute occlusion of either the internal carotid or the proximal middle cerebral artery with insufficient collateral blood flow is associated with a high case fatality rate of approximately 60%. Thus, a decompressive hemicraniectomy is considered a life-saving procedure for this devastating disease. Findings of three recent randomized, controlled clinical trials and their meta-analysis showed that early surgical decompression not only reduced the number of case fatalities but also increased the incidence of favorable outcomes. The authors review the pathophysiology, historical background in previous studies, operative timing, surgical technique and clinical outcomes of surgical decompression for malignant hemispheric infarction.
Brain edema; Cerebral infarction; Decompressive surgery; Middle cerebral artery
We recently experienced self-detachment of the Solitaire stent during mechanical thrombectomy of acute ischemic stroke. Then, we tried to remove the detached stent and to recanalize the occlusion, but failed with endovascular means. The following diffusion weighted image MRI revealed no significant increase in infarction size, therefore, we performed surgical removal of the stent to rescue the patient and to elucidate the reason why the self-detachment occurred. Based upon the operative findings, the stent grabbed the main thrombi but inadvertently detached at a severely tortuous, acutely angled, and circumferentially calcified segment of the internal carotid artery. Postoperative angiography demonstrated complete recanalization of the internal carotid artery. The patient's neurological deficits gradually improved, and the modified Rankin scale score was 2 at three months after surgery. In the retrospective case review, bone window images of the baseline computed tomography (CT) scan corresponded to the operative findings. According to this finding, we hypothesized that bone window images of a baseline CT scan can play a role in terms of anticipating difficult stent retrieval before the procedure.
CT scan; Thrombectomy; Self-detachment; Stent; Stroke
Hypothermic protection against ischemic stroke has been reported by many studies. Hypothermia is supposed to mitigate the effects of deleterious genes and proteins and promote the activity of protective genes and proteins in the ischemic brain. Metallothionein (MT)-1/2 is thought to be a crucial factor for metal homeostasis, immune function, and apoptosis. This protein was found to exert protective effects in models of brain injury as well. In the present study, we investigated the effect of hypothermia on MT expression and the underlying mechanisms.
Cultured bEnd.3 brain endothelial cells were exposed to oxygen glucose deprivation and reperfusion (OGD+R). Reverse transcription PCR and western blot analyses were performed to measure the expression of MT, transcription factors, and methylation regulating factors. Transcription factor binding assays were also performed. Methylation profiles of the promoter area were obtained with pyrosequencing.
Hypothermia protected bEnd.3 cells from OGD+R. When the cells were exposed to OGD+R, MT expression was induced. Hypothermia augmented MT levels. While OGD+R-induced MT expression was mainly associated with metal regulatory transcription factor 1 (MTF-1), MT expression promoted by hypothermia was primarily mediated by the signal transducer and activator of transcription 3 (STAT3). Significantly increased STAT3 phosphorylation at Ser727 was observed with hypothermia, and JSI-124, a STAT-3 inhibitor, suppressed MT expression. The DNA demethylating drug 5-aza-2′-deoxycytidine (5-Aza) enhanced MT expression. Some of the CpG sites in the promoter MT=> it should be “the CpG sites in the MT promoter” showed different methylation profiles and some methylation regulating factors had different expressional profiles in the presence of OGD+R and hypothermia.
We demonstrated that hypothermia is a potent inducer of MT gene transcription in brain endothelial cells, and enhanced MT expression might contribute to protection against ischemia. MT gene expression is induced by hypothermia mainly through the STAT3 pathway. DNA methylation may contribute to MT gene regulation under ischemic or hypothermic conditions.
Hypothermia; Ischemia; STAT3; MRE; Methylation; Gene expression
A superciliary keyhole approach is an attractive, minimally invasive surgical technique, yet the procedure is limited due to a small cranial opening. Nonetheless, an unruptured supraclinoid internal carotid artery (ICA) aneurysm can be an optimal surgical target of a superciliary approach as it is located in the center of the surgical view and field. Therefore, this study evaluated the feasibility and surgical outcomes of a superciliary keyhole approach for unruptured ICA aneurysms.
The authors report on a consecutive series of patients who underwent a superciliary approach for clipping unruptured ICA aneurysms between January 2007 and February 2012. The data were compared with a historical control group who underwent a pterional approach between January 2003 and December 2006.
In the superciliary group, a total of 71 aneurysms were successfully clipped without a residual sac in 70 patients with a mean age of 57 years (range, 37-75 years). The maximum diameter of the aneurysms ranged from 4 mm to 14 mm (mean±standard deviation, 6.6±2.3 mm). No direct mortality or permanent morbidity was related to the surgery. The superciliary approach demonstrated statistically significant advantages over the pterional approach, including a shorter operative duration (mean, 100 min), no intraoperative blood transfusions, and no postoperative epidural hemorrhages.
A superciliary keyhole approach provides a sufficient surgical corridor to clip most unruptured supraclinoid ICA aneurysms in a minimally invasive manner.
Cerebral aneurysm; Internal carotid artery; Minimal surgical procedure; Treatment outcome
The purposes of this study are to investigate the factors that may be related to ventriculoperitoneal (VP) shunt in patients with cerebellar hematoma and the effect of severe fourth ventricular hemorrhage, causing obstructive hydrocephalus on subsequent VP shunt performance.
This study included 31 patients with spontaneous cerebellar hematoma and concomitant fourth ventricular hemorrhage, who did not undergo a surgical evacuation of hematoma. We divided this population into two groups; the VP shunt group, and the non-VP shunt group. The demographic data, radiologic findings, and clinical factors were compared in each group. The location of the hematoma (whether occupying the cerebellar hemisphere or the vermis) and the degree of the fourth ventricular obstruction were graded respectively. The intraventricular hemorrhage (IVH) score was used to assess the IVH severity.
Ten out of 31 patients underwent VP shunt operations. The midline location of cerebellar hematoma, the grade of fourth ventricle obstruction, and IVH severity were significantly correlated with that of VP shunt operation (p=0.015, p=0.013, p=0.028). The significant variables into a logistic regression multivariate model resulted in statistical significance for the location of cerebellar hemorrhage [p=0.05; odds ratio (OR), 8.18; 95% confidence interval (CI), 1.00 to 67.0], the grade of fourth ventricle obstruction (p=0.044; OR, 19.26; 95% CI, 1.07 to 346.6).
The location of the cerebellar hematoma on CT scans and the degree of fourth ventricle obstruction by IVH were useful signs for the selection of VP shunt operation in patients with spontaneous cerebellar hematoma and concomitant acute hydrocephalus.
Cerebellar hematoma; Intraventricular hemorrhage; Hydrocephalus; Fourth ventricular obstruction
Induced therapeutic hypothermia is the one of the most effective tools against brain injury and inflammation. Even though its beneficial effects are well known, there are a lot of pitfalls to overcome, since the potential adverse effects of systemic hypothermia are still troublesome. Without the knowledge of the precise mechanisms of hypothermia, it will be difficult to tackle the application of hypothermia in clinical fields. Better understanding of the characteristics and modes of hypothermic actions may further extend the usage of hypothermia by developing novel drugs based on the hypothermic mechanisms or by combining hypothermia with other therapeutic modalities such as neuroprotective drugs. In this review, we describe the potential therapeutic targets for the development of new drugs, with a focus on signal pathways, gene expression, and structural changes of cells. Theapeutic hypothermia has been shown to attenuate neuroinflammation by reducing the production of reactive oxygen species and proinflammatory mediators in the central nervous system. Along with the mechanism-based drug targets, applications of therapeutic hypothermia in combination with drug treatment will also be discussed in this review.
Hypothermia; pharmacotherapy; drug target; signal pathway; neuroinflammation.
Therapeutic hypothermia is one of the neuroprotective strategies that improve neurological outcomes after brain damage in ischemic stroke and traumatic brain injury. Microglial cells become activated following brain injury and play an important role in neuroinflammation and subsequent brain damage. The aim of this study was to determine the time-dependent effects of hypothermia on microglial cell activation and migration, which are accompanied by neuroinflammation.
Microglial cells in culture were subjected to mild (33 °C) or moderate (29 °C) hypothermic conditions before, during, or after lipopolysaccharide (LPS) or hypoxic stimulation, and the production of nitric oxide (NO), proinflammatory cytokines, reactive oxygen species, and neurotoxicity was evaluated. Effects of hypothermia on microglial migration were also determined in in vitro as well as in vivo settings.
Early-, co-, and delayed-hypothermic treatments inhibited microglial production of inflammatory mediators to varying degrees: early treatment was the most efficient, and delayed treatment showed time-dependent effects. Delayed hypothermia also suppressed the mRNA levels of proinflammatory cytokines and iNOS, and attenuated microglial neurotoxicity in microglia-neuron co-cultures. Furthermore, delayed hypothermia reduced microglial migration in the Boyden chamber assay and wound healing assay. In a stab injury model, delayed local hypothermia reduced migration of microglia toward the injury site in the rat brain.
Taken together, our results indicate that delayed hypothermia is sufficient to attenuate microglial activation and migration, and provide the basis of determining the optimal time window for therapeutic hypothermia. Delayed hypothermia may be neuroprotective by inhibiting microglia-mediated neuroinflammation, indicating the therapeutic potential of post-injury hypothermia for patients with brain damages exhibiting some of the inflammatory components.
Hypothermia; Microglia; Cell migration; Neuroinflammation; Neuroprotection
External ventricular drain (EVD) is commonly performed with a freehand technique using surface anatomical landmarks at two different cranial sites, Kocher's point and the forehead. The aim of this study was to evaluate and compare the accuracy and safety of these percutaneous ventriculostomies.
A retrospectively review of medical records and head computed tomography scans were examined in 227 patients who underwent 250 freehand pass ventriculostomy catheter placements using two different methods at two institutions, between 2003 and 2009. Eighty-one patients underwent 101 ventriculostomies using Kocher's point (group 1), whereas 146 patients underwent 149 forehead ventriculostomies (group 2).
In group 1, the catheter tip was optimally placed in either the ipsilateral frontal horn or the third ventricle, through the foramen of Monro (grade 1) in 82 (81.1%) procedures, in the contralateral lateral ventricle (grade 2) in 4 (3.9%), and into eloquent structures or non-target cerebrospinal space (grade 3) in 15 (14.8%). Intracerebral hemorrhage (ICH) >1 mL developed in 5 (5.0%) procedures. Significantly higher incidences of optimal catheter placements were observed in group 2. ICH>1 mL developed in 11 (7.4%) procedures in group 2, showing no significant difference between groups. In addition, the mean interval from the EVD to ventriculoperitoneal shunt was shorter in group 2 than in group 1, and the incidence of EVD-related infection was decreased in group 2.
Accurate and safe ventriculostomies were achieved using both cranial sites, Kocher's point and the forehead. However, the forehead ventriculostomies provided more accurate ventricular punctures.
Computed tomography; Freehand; Hydrocephalus; Ventriculostomy
Abnormal contrast enhancement on brain computed tomography (CT) scan after diagnostic or interventional angiography is not rare, and has known to be induced by temporary blood-brain barrier (BBB) disruption from contrast media. Furthermore, it has been regarded as clinically subtle, but reported to have no symptom or mild transient symptoms. However, we recently experienced two cases of serious BBB disruption during the acute period after coiling of an unruptured intracranial aneurysm. One patient presented with an unruptured paraclinoid internal carotid artery (ICA) aneurysm on the right and the other with an unruptured right supraclinoid ICA aneurysm. Both patients showed similar findings on immediate postembolization CT scan and clinical courses after coiling. Typical radiological, clinical characteristics of BBB disruption were described. In addition, the role of immediate postembolization CT scan are also discussed.
Aneurysm; Blood-brain barrier; Coil; Embolization
Intercellular adhesion molecule-1 (ICAM-1) in cerebral vascular endothelium induced by ischemic insult triggers leukocyte infiltration and inflammatory reaction. We investigated the mechanism of hypothermic suppression of ICAM-1 in a model of focal cerebral ischemia. Rats underwent 2 hours of middle cerebral artery occlusion and were kept at 37°C or 33°C during occlusion and rewarmed to normal temperature immediately after reperfusion. Under hypothermic condition, robust activation of extracellular signal-regulated kinase-1/2 (ERK1/2) was observed in vascular endothelium of ischemic brain. Hypothermic suppression of ICAM-1 was reversed by ERK1/2 inhibition. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) in ischemic vessel was attenuated by hypothermia. STAT3 inhibitor suppressed ICAM-1 production induced by stroke. ERK1/2 inhibition enhanced phosphorylation and DNA binding activity of STAT3 in hypothermic condition. In this study, we demonstrated that hypothermic suppression of ICAM-1 induction is mediated by enhanced ERK1/2 activation and subsequent attenuation of STAT3 action.
The amount of hemorrhage observed on a brain computed tomography scan, or a patient's Fisher grade (FG), is a powerful risk factor for development of shunt dependent hydrocephlaus (SDHC). However, the influence of treatment modality (clipping versus coiling) on the rate of SDHC development has not been thoroughly investigated. Therefore, we compared the risk of SDHC in both treatment groups according to the amount of subarachnoid hemorrhage (SAH).
We retrospectively reviewed 839 patients with aneurysmal SAH for a 5-year-period. Incidence of chronic SDHC was analyzed using each treatment modality according to the FG system. In addition, other well known risk factors for SDHC were also evaluated.
According to our data, Hunt-Hess grade, FG, acute hydrocephalus, and intraventricular hemorrhage were significant risk factors for development of chronic SDHC. Coiling group showed lower incidence of SDHC in FG 2 patients, and clipping groups revealed a significantly lower rate in FG 4 patients.
Based on our data, treatment modality might have an influence on the incidence of SDHC. In FG 4 patients, the clipping group showed lower incidence of SDHC, and the coiling group showed lower incidence in FG 2 patients. We suggest that these findings could be a considerable factor when deciding on a treatment modality for aneurysmal SAH patients, particularly when the ruptured aneurysm can be occluded by either clipping or coiling.
Shunt dependent hydrocephalus; Fisher grading system; Subarachnoid hemorrhage
While a delayed intracerebral hemorrhage at the site of a ventricular catheter has occasionally been reported in literature, a delayed hemorrhage caused by venous infarction secondary to ventriculoperitoneal shunting has not been previously reported. In the present case, a 68-year-old woman underwent ventriculoperitoneal shunting through a frontal burr hole, and developed a hemorrhagic transformation of venous infarction on the second postoperative day. This massive venous infarction was caused by bipolar coagulation and occlusion of a large paramedian cortical vein in association with atresia of the rostral superior sagittal sinus. Thus, to eliminate the risk of postoperative venous infarction, technical precautions to avoid damaging surface vessels in a burr hole are required under loupe magnification in ventriculoperitoneal shunting.
Hydrocephalus; Intracerebral hemorrhage; Postoperative complication; Venous infarction; Ventriculoperitoneal shunt
Vertebral artery (VA) injury is a rare and serious complication of cervical spine surgery; this is due to difficulty in controlling hemorrhage, which can result in severe hypotension and cardiac arrest, and uncertain neurologic consequences. The authors report an extremely rare case of a 56-year-old woman who underwent direct surgical repair by end-to-end anatomosis of an unanticipated VA injury during C2 pedicle screwing. Postoperatively, the patient showed no neurological deterioration and computed tomography angiography of the VA demonstrated normal blood flow. Although direct occlusion of an injured VA by surgical ligation or endovascular embolization has been used for management of an unanticipated VA injury during surgery, these methods may be associated with significant morbidity and mortality. However, despite its technical demand, microvascular primary repair can restore normal blood flow and minimizes the risk of immediate or delayed ischemic complications. Here we report an iatrogenic VA injury during C2 pedicle screwing, which was successfully treated by end-to-end anastomosis.
Vertebral artery injury; End-to-end anastomosis; Atlantoaxial complex
Accessory middle cerebral artery (MCA) is an infrequent vascular anomaly of the brain. Cerebral aneurysms associated with this anomalous artery are also very rare. To our knowledge, there have only been ten previous reports of an aneurysm associated with accessory MCA. The authors present two patients with accessory MCA-related aneurysms. A 38-year-old male and a 59-year-old female both presented with sudden-onset severe headache. In both patients, computed tomography (CT) scan revealed subarachnoid hemorrhage. A subsequent angiogram demonstrated an accessory MCA arising from the anterior cerebral artery (ACA) and a saccular aneurysm at the anterior communicating artery (ACoA) complex associated with an accessory MCA. Surgical clipping allowed for complete exclusion of the aneurysm from the arterial circulation. Based on our review of the ten cases of aneurysms associated with accessory MCA documented in the literature, we suggest that accessory MCA-related aneurysms can be classified according to whether the accessory MCA originates from the proximal A1 segment or from the ACoA complex. We also emphasize the importance of precise interpretation of preoperative angiograms and intraoperative precaution in determining the presence of this anomalous artery prior to temporary clip placement.
Accessory middle cerebral artery; Aneurysm; Anterior communicating artery complex
Medpor porous polyethylene was used to reconstruct small bone defects (gaps and burr holes) along a craniotomy bone flap. The feasibility and cosmetic results were evaluated.
Medpor Craniotomy Gap Wedges, V and T, were designed. The V implant is a 10 cm-long wedge strip, the cross section of which is an isosceles triangle with a 4 mm-long base, making it suitable for gaps less than 4 mm after trimming. Meanwhile, the Medpor T wedge includes a 10 mm-wide thin plate on the top surface of the Medpor V Wedge, making it suitable for gaps wider than 4 mm and burr holes. Sixty-eight pterional craniotomies and 39 superciliary approaches were performed using the implants, and the operative results were evaluated with respect to the cosmetic results and pain or tenderness related to the cranial flap.
The small bone defects were eliminated with less than 10 minutes additional operative time. In a physical examination, there were no considerable cosmetic problems regarding to the cranial bone defects, such as a linear depression or dimple in the forehead, anterior temporal hollow, preauricular depression, and parietal burr hole defect. Plus, no patient suffered from any infectious complications.
The Medpor Craniotomy Gap Wedge is technically easy to work with for reconstructing small bone defects, such as the bone gaps and burr holes created by a craniotomy, and produces excellent cosmetic results.
Cosmetic appearance; Craniotomy; Medpor; Operative technique
Remote cerebellar hemorrhage (RCH) is one of the rare complications occurring after supratentorial surgery, and its pathomechanism is poorly understood. We report 10 cases of RCH from our institution and review 154 cases from a database in order to delineate incidence, common presentation, risk factors, and outcomes of this complication. In addition, the means of prevention are discussed.
We reviewed the medical records of 10 patients who experienced RCH after undergoing supratentorial surgery at our institution between 2001 and 2008. A database search in Medline revealed 154 cases of RCH in the English literature. Characteristic features were analyzed and compared.
There were 10 cases of RCH among 3307 supratentorial surgery cases, indicating a 0.3% incidence. All patients had characteristic imaging features of RCH, namely a streaky bleeding pattern in the superior folia of the cerebellum. Seven patients had a history of preoperative hypertension. Four cases were related to cerebral aneurysms, and other four developed after the removal of brain tumors. Cerebrospinal fluid (CSF) drainage apparatuses were installed postoperatively in all cases. Outcomes according to modified Rankin scale (mRS) were good in 7 patients, with 1 fatal case.
RCH is a rare complication after supratentorial surgery, and the exact etiology still remains uncertain. Hypertension and perioperative loss of CSF seem positively correlated with RCH, but no single risk factor is totally responsible. Patients with RCH should be closely observed to improve their prognosis.
Remote cerebellar hemorrhage; Supratentorial surgery; CSF drainage
A case of large aneurysm arising from the distal end of an azygous A2 segment is presented. Multiple clip application inadvertently tore the aneurysmal neck, resulting in near avulsion of a right pericallosal artery origin. After an unsuccessful attempt to repair the avulsion, it was treated by occlusion of the origin of the pericallosal artery and an A4-A4 anterior cerebral artery in situ bypass without neurological deficits. The surgical technique and previous reports on side-to-side in situ bypass are discussed.
Aneurysm; Azygous anterior cerebral artery; In situ bypass procedure; Pericallosal artery
In order to assess the incidence of thromboembolic events and their clinical presentations, the present study prospectively examined routine brain magnetic resonance images (MRI) taken within 48 hours after a coil embolization of cerebral aneurysms.
From January 2006 to January 2008, 163 cases of coil embolization of cerebral aneurysm were performed along with routine brain MRI, including diffusion-weighted magnetic resonance (DW-MR) imaging, within 48 hours after the embolization of the aneurysm to detect the silent thromboembolic events regardless of any neurological changes. If any neurological changes were observed, an immediate brain MRI follow-up was performed. High-signal-intensity lesions in the DW-MR images were considered as acute thromboembolic events and the number and locations of the lesions were also recorded.
Among the 163 coil embolization cases, 98 (60.1%) showed high-signal intensities in the DW-MR imaging follow-up, 66 cases (67.0%) involved the eloquent area and only 6 cases (6.0%) showed focal neurological symptoms correlated to the DW-MR findings. The incidence of DW-MR lesions was higher in older patients (≥60 yrs) when compared to younger patients (<60 yrs) (p=0.002, odd's ratio=1.043). The older patients also showed a higher incidence of abnormal DW-MR signals in aneurysm-unrelated lesions (p=0.0003, odd's ratio=5.078).
The incidence of symptomatic thromboembolic attacks after coil embolization of the cerebral aneurysm was found to be lower than that reported in previous studies. While DW-MR imaging revealed a higher number of thromboembolic events, most of these were clinically silent and transient and showed favorable clinical outcomes. However, the incidence of DW-MR abnormalities was higher in older patients, along with unpredictable thromboembolic events on DW-MR images. Thus, in order to provide adequate and timely treatment and to minimize neurological sequelae, a routine DW-MR follow-up after coil embolization of cerebral aneurysms might be helpful, especially in older patients.
Cerebral aneurysm; Embolization; Thromboembolism; Diffusion magnetic resonance imaging
Repeated administration of mannitol in the setting of large hemispheric infarction is a controversial and poorly defined therapeutic intervention. This study was performed to examine the effects of multiple-dose mannitol on a brain edema after large hemispheric infarction.
A middle cerebral artery was occluded with the rat suture model for 6 hours and reperfused in 22 rats. The rats were randomly assigned to either control (n=10) or the mannitol-treated group (n=12) in which intravenous mannitol infusions (0.8 g/kg) were performed six times every four hours. After staining a brain slice with 2,3,5-triphenyltetrazolium chloride, the weight of hemispheres, infarcted (IH) and contralateral (CH), and the IH/CH weight ratio were examined, and then hemispheric accumulation of mannitol was photometrically evaluated based on formation of NADH catalyzed by mannitol dehydrogenase.
Mannitol administration produced changes in body weight of -7.6±1.1%, increased plasma osmolality to 312±8 mOsm/L. It remarkably increased weight of IH (0.77±0.06 gm versus 0.68±0.03 gm : p<0.01) and the IH/CH weight ratio (1.23±0.07 versus 1.12±0.05 : p<0.01). The photometric absorption at 340 nm of the cerebral tissue in the mannitol-treated group was increased to 0.375±0.071 and 0.239±0.051 in the IH and CH, respectively from 0.167±0.082 and 0.162±0.091 in the IH and CH of the control group (p<0.01).
Multiple-dose mannitol is likely to aggravate cerebral edema due to parenchymal accumulation of mannitol in the infarcted brain tissue.
Brain edema; Cerebral infarction; Mannitol; Mannitol dehydrogenase; Rat; Middle cerebral artery
In the present study, we exploited the superior features of peptide nucleic acids (PNAs) to develop an efficient PNA zip-code microarray for the detection of hepatocyte nuclear factor-1α (HNF-1α) mutations that cause type 3 maturity onset diabetes of the young (MODY). A multi-epoxy linker compound was synthesized and used to achieve an efficient covalent linking of amine-modified PNA to an aminated glass surface. PCR was performed to amplify the genomic regions containing the mutation sites. The PCR products were then employed as templates in a subsequent multiplex single base extension reaction using chimeric primers with 3′ complementarity to the specific mutation site and 5′ complementarity to the respective PNA zip-code sequence on the microarray. The primers were extended by a single base at each corresponding mutation site in the presence of biotin-labeled ddNTPs, and the products were hybridized to the PNA microarray. Compared to the corresponding DNA, the PNA zip-code sequence showed a much higher duplex specificity for the complementary DNA sequence. The PNA zip-code microarray was finally stained with streptavidin-R-phycoerythrin to generate a fluorescent signal. Using this strategy, we were able to correctly diagnose several mutation sites in exon 2 of HNF-1α with a wild-type and mutant samples including a MODY3 patient. This work represents one of the few successful applications of PNA in DNA chip technology.