Microsurgical anatomy of the posterior median septum of the human spinal cord.

The aim of this study was to analyze the topographical anatomy of the dorsal spinal cord (SC) in relation to the posterior median septum (PMS). This included the course and variations in the PMS, and its relationship to and distance from other dorsal spinal landmarks. Microsurgical anatomy of the PMS was examined in 12 formalin-fixed adult cadaveric SCs. Surface landmarks such as the dorsal root entry zone (DREZ), the denticulate ligament, the architecture of the leptomeninges and pial vascular distribution were noted. The PMS was examined histologically in all spinal segments. The PMS extended most deeply at spinal segments C7 and S4. This was statistically significant for all spinal segments except C5. The PMS was shallowest at segments T4 and T6, where it was statistically significantly thinner than at any other segment. In 80% of the SCs, small blood vessels were identified that traveled in a rostrocaudal direction in the PMS. The longest distance between the PMS and the DREZ was at the C1-C4 vertebral levels and the shortest distance was at the S5 level. Prevention of deficits following a dorsal midline neurosurgical approach to deep-seated SC lesions requires careful identification of the midline of the cord. The PMS and septum define the midline on the dorsum of the SC and their accurate identification is essential for a safe midline surgical approach. In this anatomical study, we describe the surface anatomy of the dorsal SC and its relationship with the PMS, which can be used to determine a safe entry zone into the SC.

A stepwise illustration of the translabyrinthine approach to a large cystic vestibular schwannoma.

Of the presigmoid approaches, the translabyrinthine approach is often used when a large exposure is needed to gain access to the cerebellopontine angle but when hearing preservation is not a concern. At the authors' institution, this approach is done with the aid of ENT/otolaryngology for temporal bone drilling and exposure. In the present article and video, the authors demonstrate the use of the translabyrinthine approach for resection of a large cystic vestibular schwannoma, delineating the steps of positioning, opening, temporal bone drilling, tumor resection, and closure. Gross-total resection was achieved in the featured case. The patient's postoperative facial function was House-Brackmann Grade II on the side ipsilateral to the tumor, although function improved with time. The translabyrinthine route to the cerebellopontine angle is an excellent approach for masses that extend toward the midline or anterior to the pons. Although hearing is sacrificed, facial nerve function is generally spared.

Microsurgical anatomy of the dorsal thoracic rootlets and dorsal root entry zones.

BACKGROUND: For successful DREZ (dorsal root entry zone) surgery, optimal neuroanatomical orientation and precise microsurgical dissection are required. Although cervical, lumbar, and sacral spinal segments have been studied in detail, such information is not available for thoracic segments. The objective of this anatomical study is to comprehensively illustrate the microanatomical features of the thoracic DREZs and their variations. METHODS: Fifteen formalin-fixed adult cadaveric spinal cords from T1 to T12 were used. The dorsal rootlet numbers, distance between the posteromedial and posterolateral sulcus, length of each DREZ, length of each segment, and mean length of the dorsal rootlets were measured under a surgical microscope. RESULTS: The longest DREZs were observed at the T6, T7, and T8 segments with mean values of 15.3 mm, 15.6 mm, and 15.4 mm, respectively. The longest segment was observed at the T10 segment with a mean value of 21.0 mm, and the shortest segment was observed at the T1 segment with a mean value of 13.5 mm. CONCLUSIONS: The highest dorsal rootlet density is at the T1 segment of the spinal cord, can be easily distinguished visually, and may be a useful surgical landmark. The DREZs in T6-7 segments are longest, while these two segments have the least number of rootlets. Because the dorsolateral tract is remarkably narrow and the dorsal horn is exceedingly deep, DREZ surgery at the thoracic level may be difficult and risky for the dorsal column and corticospinal tract. Acquaintance with the microanatomy of the DREZ in the thoracic spinal cord is crucial to DREZ surgery.

Chronic neurological deficits in mice after perinatal hypoxia and ischemia correlate with hemispheric tissue loss and white matter injury detected by MRI.

We investigated the effects of perinatal hypoxia-ischemia (HI) on brain injury and neurological functional outcome at postnatal day (P)30 through P90. HI was induced by exposing P9 mice to 8% O(2) for 55 min using the Vannucci HI model. Following HI, mice were treated with either vehicle control or Na(+)/H(+) exchanger isoform 1 (NHE1) inhibitor HOE 642. The animals were examined by the accelerating rotarod test at P30 and the Morris water maze (MWM) test at P60. T(2)-weighted MRI was conducted at P90. Diffusion tensor imaging (DTI) was subsequently performed in ex vivo brains, followed by immunohistochemical staining for changes in myelin basic protein (MBP) and neurofilament protein expression in the corpus callosum (CC). Animals at P30 after HI showed deficits in motor and spatial learning. T(2) MRI detected a wide spectrum of brain injury in these animals. A positive linear correlation was observed between learning deficits and the degree of tissue loss in the ipsilateral hemisphere and hippocampus. Additionally, CC DTI fractional anisotropy (FA) values correlated with MBP expression. Both FA and MBP values correlated with performance on the MWM test. HOE 642-treated mice exhibited improved spatial learning and memory, and less white matter injury in the CC. These findings suggest that HI-induced cerebral atrophy and CC injury contribute to the development of deficits in learning and memory, and that inhibition of NHE1 is neuroprotective in part by reducing white matter injury. T(2)-weighted MRI and DTI are useful indicators of functional outcome after perinatal HI.

Level I to III craniofacial approaches based on Barrow classification for treatment of skull base meningiomas: surgical technique, microsurgical anatomy, and case illustrations.

OBJECT: Although craniofacial approaches to the midline skull base have been defined and surgical results have been published, clear descriptions of these complex approaches in a step-wise manner are lacking. The objective of this study is to demonstrate the surgical technique of craniofacial approaches based on Barrow classification (Levels I-III) and to study the microsurgical anatomy pertinent to these complex craniofacial approaches. METHODS: Ten adult cadaveric heads perfused with colored silicone and 24 dry human skulls were used to study the microsurgical anatomy and to demonstrate craniofacial approaches in a step-wise manner. In addition to cadaveric studies, case illustrations of anterior skull base meningiomas were presented to demonstrate the clinical application of the first 3 (Levels I-III) approaches. RESULTS: Cadaveric head dissection was performed in 10 heads using craniofacial approaches. Ethmoid and sphenoid sinuses, cribriform plate, orbit, planum sphenoidale, clivus, sellar, and parasellar regions were shown at Levels I, II, and III. In 24 human dry skulls (48 sides), a supraorbital notch (85.4%) was observed more frequently than the supraorbital foramen (14.6%). The mean distance between the supraorbital foramen notch to the midline was 21.9 mm on the right side and 21.8 mm on the left. By accepting the middle point of the nasofrontal suture as a landmark, the mean distances to the anterior ethmoidal foramen from the middle point of this suture were 32 mm on the right side and 34 mm on the left. The mean distance between the anterior and posterior ethmoidal foramina was 12.3 mm on both sides; the mean distance between the posterior ethmoidal foramen and distal opening of the optic canal was 7.1 mm on the right side and 7.3 mm on the left. CONCLUSIONS: Barrow classification is a simple and stepwise system to better understand the surgical anatomy and refine the techniques in performing these complex craniofacial approaches. On the other hand, thorough anatomical knowledge of the midline skull base and variations of the neurovascular structures is crucial to perform successful craniofacial approaches.

Microsurgical anatomy of the vein of Labbé.

OBJECTIVE: Venous drainage of the temporal lobe is of great importance in various neurosurgical and combined skull base approaches. The most significant draining vein of the temporal lobe is the inferior anastomotic vein (vein of Labbé). The purpose of this study was to examine the detailed anatomy and variations of the vein of Labbé (VL) from microsurgical perspective. METHODS: Fourteen fixed human cadaver heads (28 sides) with perfused vessels were included to define microsurgical anatomy and variations of the VL. RESULTS: The main findings of the present study were as follows: (1) drainage pattern of the VL was found to be very variable in cadaveric dissections; (2) VL drained around the sinus confluence at the tentorium in one specimen (3.5%), into the large meningeal vein in the occipital dura mater in another specimen (3.5%). The VL rarely (7%) drains into the superior petrosal sinus (SPS) which may make combined skull base approaches very difficult or impossible. CONCLUSION: Results of this study suggest that careful and thorough evaluation of the VL is of great importance, especially in surgeries combining a subtemporal route with petrosal approaches by sectioning the SPS and the tentorium.

Woven EndoBridge device for ruptured aneurysms: perioperative results of a US multicenter experience.

BACKGROUND: The Woven EndoBridge (WEB) device is approved in the USA for treatment of unruptured wide-neck bifurcation aneurysms. However, the safety and effectiveness of the WEB device in the treatment of ruptured intracranial aneurysms is not clear. We aim to evaluate the perioperative safety and effectiveness of the WEB device in patients with ruptured intracranial aneurysms. METHODS: This retrospective study, conducted at eight centers in the USA, included patients with ruptured intracranial aneurysms treated with the WEB device in the setting of subarachnoid hemorrhage (SAH). Safety outcomes included intraoperative complications such as vessel perforation, thromboembolic events, and postoperative hemorrhagic or thromboembolic complications based on radiologic imaging. The primary effectiveness outcome was adequate (complete and neck remnant) aneurysm occlusion, according to the Raymond-Roy classification. RESULTS: A total of 91 patients with 94 ruptured intracranial aneurysms were included (mean age 57.7±15.2 years; 68.1% women; 82.9% wide-necked). Aneurysms were located in the anterior communicating artery (42/94, 44.6%), middle cerebral artery (16/94, 17%), and basilar artery (15/94, 16%). Adequate occlusion was achieved in 48.8% (41/84) and 80.0% (40/50) at discharge and last follow-up (mean of 3.4 months), respectively. At discharge, procedural-related morbidity was 3.3% (3/91) and there was no procedure-related mortality. No re-rupture or delayed aneurysm rupture was observed. CONCLUSIONS: This study demonstrates the perioperative safety and effectiveness of the WEB device for the treatment of patients with ruptured intracranial aneurysms in the setting of SAH, with low periprocedural morbidity and mortality. Long-term follow-up is warranted.

Defining a new neurosurgical complication classification: lessons learned from a monthly Morbidity and Mortality conference.

OBJECTIVEThe absence of a commonly accepted standardized classification system for complication reporting confounds the recognition, objective reporting, management, and avoidance of perioperative adverse events. In the past decade, several classification systems have been proposed for use in neurosurgery, but these generally focus on tallying specific complications and grading their effect on patient morbidity. Herein, the authors propose and prospectively validate a new neurosurgical complication classification based on understanding the underlying causes of the adverse events.METHODSA new complication classification system was devised based on the authors' previous work on morbidity in endovascular surgery. Adverse events were prospectively compiled for all neurosurgical procedures performed at their tertiary care academic medical center over the course of 1 year into 5 subgroups: 1) indication errors; 2) procedural errors; 3) technical errors; 4) judgment errors; and 5) critical events. The complications were presented at the monthly institutional Morbidity and Mortality conference where, following extensive discussion, they were assigned to one of the 5 subgroups. Additional subgroup analyses by neurosurgical subspecialty were also performed.RESULTSA total of 115 neurosurgical complications were observed and analyzed during the study period. Of these, nearly half were critical events, while technical errors accounted for approximately one-third of all complications. Within neurosurgical subspecialties, vascular neurosurgery (36.5%) had the most complications, followed by spine & peripheral nerve (21.7%), neuro-oncology (14.8%), cranial trauma (13.9%), general neurosurgery (12.2%), and functional neurosurgery (0.9%).CONCLUSIONSThe authors' novel neurosurgical complication classification system was successfully implemented in a prospective manner at their high-volume tertiary medical center. By employing the well-established Morbidity and Mortality conference mechanism, this simple system may be easily applied at other neurosurgical centers and may allow for uniform analyses of perioperative morbidity and the introduction of corrective initiatives.

Tenosynovial Giant Cell Tumor of the Clinoid: Rare Condition.

BACKGROUND: A tenosynovial giant cell tumor (TGCT) is a rare type of tumor that primarily arises from the tendon sheath, synovium, and bursae. In rare cases, these tumors can affect joints of the head and neck such as the temporomandibular joint. This is the only case to our knowledge of an intracranial TGCT tumor of the clinoid. CASE DESCRIPTION: We present the case of a 25-year-old female with a 2-year history of progressively blurred vision in her left eye without visual field defects. She denied any headaches or symptoms referable to the left eye region. Past medical history was significant for meningitis at 10 months of age. Family history was noncontributory with no history of brain tumors. CONCLUSIONS: A tumor originating from the left anterior clinoid was found intraoperatively and confirmed by histology to be a TGCT.

Microcystic/Reticular Schwannoma of the Frontal Lobe: An Unusual Occurrence.

Schwannoma is a benign peripheral nerve sheath tumor that typically involves cranial nerves of the head and neck region. Intraparenchymal occurrence of this tumor is uncommon. Even rarer in this site is the microcystic/reticular pattern of schwannoma. This histologic variant, first described in 2008, has a predilection for visceral organs. Herein, we report the first case of microcystic/reticular schwannoma of the frontal lobe.

Monitoring Ischemic Cerebral Injury in Spontaneously Hypertensive Rats by Diffusion Tensor Imaging.

AIM: We have applied diffusion tensor imaging (DTI) to interrogate microstructural changes in white matter integrity in a widely used middle cerebral artery occlusion (MCAO) model of cerebral ischemia. MATERIAL AND METHODS: We performed ex vivo DTI 35 days after 60 minutes transient focal ischemia in male spontaneously hypertensive rats and generated fractional anisotropy (FA), mean, axial and radial diffusivity maps. Regions of interest corresponding to external capsule (EC), corpus callosum (CC) and internal capsule (IC) were compared among sham and stroked rats. We compared tractographic projections of white matter fiber patterns and examined white matter integrity by Luxol fast blue histological analysis. We also determined infarct lesion volumes at 24 hours post-ischemia by T2-weighted magnetic resonance imaging (MRI) or at 35 days by histological staining with cresyl violet. RESULTS: We found alterations in EC and IC, but not CC, as represented by decreased FA and increased mean, axial and radial diffusivities. The size of the ischemic lesion detected subacutely by T2-weighted MRI or at 35 days by histological staining correlated with the decline in FA in the affected structures. Tractography revealed disruption of fiber trajectories through the EC and reorientation of fibers within the caudate/putamen of rats subjected to MCAO. Similarly, loss of white matter integrity in the EC and increased white matter density in the caudate/putamen along the infarct border zone was evidenced by Luxol fast blue staining. CONCLUSION: Diffusion tensor imaging therefore allows for monitoring of white matter injury and reorganization in hypertensive rats.

Atypical meningioma: randomized trials are required to resolve contradictory retrospective results regarding the role of adjuvant radiotherapy.

BACKGROUND: The role of postoperative radiation (RT) in atypical meningioma remains controversial. MATERIALS AND METHODS: We report a retrospective review of outcomes and prognostic factor analysis in 158 patients treated between 2000 and 2010, and extensively review the literature. RESULTS: Following resection, 23 patients received immediate RT, whereas 135 did not. Median progression-free survival (PFS) with and without RT was 59 (range 43-86) and 88 (range 64-123) months. For Simpson grade (G) 1-3 resection, with and without RT, median PFS was 48 (2-80) versus 96 (88-123) months and for Simpson G4, it was 59 (6-86) versus 47 (15-104) months (P = 0.4). The rate of 5-year overall survival (OS) with and without RT was 89% and 83%, respectively. On univariate analysis, Simpson G4 (HR 3.2, P = 0.0006) and brain invasion (HR 2.2, P = 0.03) were significantly associated with progression, whereas age >60 years (HR 9.7, P = 0.002), mitoses >5 per 10 high-power field (0.2, P = 0.0056), and Simpson G4 (HR 2.4, P = 0.07) were associated with higher risk of death. We summarized 22 additional reports, which provide very divergent results regarding the benefit of RT. CONCLUSIONS: In our series, adjuvant RT is surprisingly associated with worse PFS and OS, and this is more likely to be due to selection bias of referring tumors with more aggressive characteristics such as elevated Ki-67 and brain invasion for adjuvant RT, rather than a direct causal effect of adjuvant RT. Although there is a trend toward improved PFS with adjuvant RT after subtotal resection, no improvement was noted in OS. Multivariate analysis did not yield statistical significance for any of the factors including Simpson grades of resection, adjuvant RT, or six pathological defining features. The relatively divergent results in the literature are most likely explained by patient selection variability; therefore, randomized trials to adequately address this question are clearly necessary.

Neuroangiography simulation using a silicone model in the angiography suite improves trainee skills.

PURPOSE: Simulation techniques in neurosurgical training are becoming more important. The purpose of this study was to determine whether silicone vascular models used in the angiography suite can render improvement in trainee performance and safety in neuroendovascular procedures. METHODS: 10 residents from neurosurgery and radiology training programs were asked to perform a diagnostic angiogram on a silicone based vascular model (United Biologics, Tustin, USA). This was done in the angiography suite with the full biplane fluoroscopy machine (Siemens, Munich, Germany). On their first attempt, they were coached by a faculty member trained in endovascular neurosurgery; on their second attempt, they received coaching only if the procedure had stalled. Technique was scored on multiple criteria by the faculty, and total time and fluoroscopy time were recorded on both attempts. RESULTS: In this group of 10 residents, overall procedure time significantly decreased from 51 to 42 min (p=0.01), and total fluoro time significantly decreased from 12 to 9 min (p=0.002) between the first attempt and the second attempt. Technical skill increased significantly in navigation, vessel selection, projection setup, and road map usage. CONCLUSIONS: Silicone vascular models used in the angiography suite, with the clinical working tools and biplane fluoroscopy, provide a valuable experience for training residents in diagnostic angiography, and improved performance and safety.

Microsurgical anatomy and variations of the anterior clinoid process.

AIM: The aim of this study was to better define the microsurgical anatomy of the supra/parasellar region and describe variations of the anterior clinoid process (ACP). MATERIAL AND METHODS: Fifteen formalin-fixed cadaver heads and 25 dry skulls were used to define the microsurgical anatomy of the ACP and related structures. The presence of the caroticoclinoid foramen (CaCF) as well as other relevant measurements were all noted. Radiological examination of the CaCF was also demonstrated on dry skulls. RESULTS: Interosseous bridges, which form between the anterior and middle clinoid processes or connect all three (anterior, middle and posterior) clinoid processes, were found in 30% of the specimens. The average basal width, length and thickness of the ACP were 7.3 mm, 9.7 mm and 5.4 mm, respectively. Length of the optic nerve (ON) up to the falciform ligament (FL) was 10.9 mm; length of the ON under the FL was 2.7 mm; length of ON after removal of the ACP and unroofing the optic canal was 21.1 mm. CONCLUSION: This study contributes to the relationship of important vascular, neural, bone and dural layers of this region and also demonstrates the variations of ACP by means of microsurgical dissections and radiological examinations.

Sustained Na+/H+ exchanger activation promotes gliotransmitter release from reactive hippocampal astrocytes following oxygen-glucose deprivation.

Hypoxia ischemia (HI)-related brain injury is the major cause of long-term morbidity in neonates. One characteristic hallmark of neonatal HI is the development of reactive astrogliosis in the hippocampus. However, the impact of reactive astrogliosis in hippocampal damage after neonatal HI is not fully understood. In the current study, we investigated the role of Na(+)/H(+) exchanger isoform 1 (NHE1) protein in mouse reactive hippocampal astrocyte function in an in vitro ischemia model (oxygen/glucose deprivation and reoxygenation, OGD/REOX). 2 h OGD significantly increased NHE1 protein expression and NHE1-mediated H(+) efflux in hippocampal astrocytes. NHE1 activity remained stimulated during 1-5 h REOX and returned to the basal level at 24 h REOX. NHE1 activation in hippocampal astrocytes resulted in intracellular Na(+) and Ca(2+) overload. The latter was mediated by reversal of Na(+)/Ca(2+) exchange. Hippocampal astrocytes also exhibited a robust release of gliotransmitters (glutamate and pro-inflammatory cytokines IL-6 and TNFα) during 1-24 h REOX. Interestingly, inhibition of NHE1 activity with its potent inhibitor HOE 642 not only reduced Na(+) overload but also gliotransmitter release from hippocampal astrocytes. The noncompetitive excitatory amino acid transporter inhibitor TBOA showed a similar effect on blocking the glutamate release. Taken together, we concluded that NHE1 plays an essential role in maintaining H(+) homeostasis in hippocampal astrocytes. Over-stimulation of NHE1 activity following in vitro ischemia disrupts Na(+) and Ca(2+) homeostasis, which reduces Na(+)-dependent glutamate uptake and promotes release of glutamate and cytokines from reactive astrocytes. Therefore, blocking sustained NHE1 activation in reactive astrocytes may provide neuroprotection following HI.

Intracranial blastomycosis presenting as an enhancing cerebellopontine mass.

Isolated Blastomyces dermatitidis infection of the central nervous system is an uncommonly encountered entity. If left untreated it can be fatal; thus accurate diagnosis in a timely manner is critical. A 37-year-old white male presented with a severe headache. An MRI scan revealed a right-sided enhancing cerebellopontine angle mass with extension into the internal acoustic canal and diffuse basilar enhancement. After thorough assessment of the patient, an open surgical biopsy of the lesion was performed for pathological evaluation. The biopsy demonstrated broad-based budding yeasts. The cerebrospinal fluid antigen enzyme immunoassay (EIA) (MVista®) for Blastomyces dermatitidis was also positive with a level of 4.28 EIA units.

How reliable and accurate is indocyanine green video angiography in the evaluation of aneurysm obliteration?

INTRODUCTION: Indocyanine green video angiography (ICG-VA) has been recently introduced into neurovascular surgery and gained a role in assessing vessel patency and obliteration of intracranial aneurysms (IA) after clipping. Although its correlation with intra-postoperative angiography was demonstrated in previous studies, difficulties in evaluating aneurysm obliteration have not been reported. We report reliability and accuracy of ICG-VA in 109 clipped aneurysms with attention given to five cases in which ICG-VA evaluation resulted in false indication that aneurysms were secure in terms of complete obliteration. MATERIALS AND METHODS: A retrospective chart review was performed of IAs surgically treated by a single surgeon from January 2009. In all cases, aneurysm obliteration was confirmed by a combination of microdoppler ultrasonography (MUSG), ICG-VA, and post-operative angiography. RESULTS: ICG-VA appropriately assessed vessel patency and aneurysm obliteration in 93.5% of aneurysms clipped. In four cases (3.6%), puncturing the dome of the aneurysm after satisfactory clipping revealed persistent flow within the aneurysm despite ICG-VA showing no flow after clipping. In one case (0.9%), ICG-VA showed persistent flow within the aneurysm and MUSG did not, and puncture of the dome confirmed no flow within the aneurysm. In one case (0.9%), ICG-VA failed to demonstrate residual neck. CONCLUSION: ICG-VA is a simple and safe procedure and an important adjunct to microsurgical clipping of aneurysm. Although ICG-VA assesses vessel patency and obliteration of aneurysms in most cases, applying the principles of microsurgery in aneurysm clipping remains a main tool for obtaining the complete obliteration of aneurysm along with preservation of the normal vasculature.

Convection enhanced delivery to the Brain: preparing for gene therapy and protein delivery to the Brain for functional and restorative Neurosurgery by understanding low-flow neurocatheter infusions using the Alaris(®) system infusion pump.

BACKGROUND: Convection enhanced delivery (CED) is an emerging form of direct brain infusion therapy employed in human functional and restorative neurosurgery clinical trials delivering protein, viral vectors for gene therapy, and siRNA. PURPOSE: Pressure monitoring has become a vital tool in ensuring infusion safety and success. We report details of this benchmark first trial of the use of a leading syringe infusion pump system capable of low-flow infusions. METHODS: Low-flow infusion performance of the FDA approved Alaris® System syringe pump, commonly used at our institution, was assessed during in vitro and ex vivo CED infusions. In vitro infusion cloud morphology and line pressure were analyzed utilizing a neuroinfusion catheter and delivering volumes and flow rates proposed for a human gene therapy protocol for Parkinson's disease. RESULTS: Pressure monitoring results correlated with previously published in-line pressure monitoring results however the time to peak with catheter occlusion was extended due to the method of pressure monitoring with this device. CONCLUSION: MRI compatible infusion pumps used for brain delivery injectables, pressure monitoring is set to be a guiding instrument for the health care professional employing this emerging form of infusion-to-brain delivery. Further development of infusion pump technology is warranted to allow for infuse/withdraw mode, infusion pressure graphical and numerical display, and pressure monitoring without the need for an inflatable reservoir pressure device. MRI safe infusion systems will need to be available and nursing staff educated to prepare infusions within the high-field environment.

Age-dependent microglial activation in immature brains after hypoxia- ischemia.

In the present study, we tested whether the ongoing differentiation of microglia in the immature brain results in more robust microglial activation and pro-inflammatory responses than juvenile brains following hypoxia-ischemia (HI). Under normoxic conditions, microglial activation profiles were assessed in postnatal day 9 and postnatal day 30 mice (P9 and P30) by analyzing relative expression levels of CD45 in CD11b+/CD45+ microglia/macrophages. Flow cytometry analysis revealed that the hippocampi of P9 and P30 brains exhibited higher levels of CD45 expression in CD11b+/CD45+ cells than in the cortex and striatum. In response to HI, there was an early increase in number of CD11b+/CD45+ microglia/macrophages in the ipsilateral hippocampus of P9 mice. These cells transformed from a "ramified" to an "amoeboid" morphology in the CA1 region, which was accompanied by a loss of microtubule-associated protein 2 immunostaining in this brain region. The peak response of microglial activation in the ipsilateral hippocampus of P9 mice occurred on day 2 post-HI, which was in contrast to a delayed and persistent microglial activation in the cortex and striatum (peak on day 9 post-HI). P9 brains demonstrated a 2-3 fold greater increase in microglia counts than P30 brains in each region (hippocampus, cortex, and striatum) during day 1-17 post-HI. P9 brains also showed more robust expression of pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1ß) than P30 brains. Taken together, compared to P30 mice, P9 mice demonstrated differences in microglial activation and pro-inflammatory responses after HI, which may be important in brain damage and tissue repair.

Demographic, circadian, and climatic factors in non-aneurysmal versus aneursymal subarachnoid hemorrhage.

BACKGROUND: Although, the relationship of spontaneous subarachnoid hemorrhage (SAH) to climatic or circadian factors has been widely studied, epidemiologic, circardian and climatic factors in non-aneurysmal SAH (naSAH), particularly perimesencephalic SAH (PMH), has not been reported before. OBJECTIVE: For the first time, demographic, climatic, and circadian variables are examined together as possible contributing factors comparing aSAH and naSAH. METHODS: We reviewed records for 384 patients admitted to University of Wisconsin Neurosurgery Service from January 2005 to December 2010 with spontaneous non-traumatic SAH. Patients were grouped as aSAH (n=338) or naSAH (n=46) on clinical and radiological criteria. PMH (n=32) was identified as a subgroup of naSAH based on radiological criteria. We logged demographic data, time of SAH, temperature at onset and atmospheric pressure at onset. The three subgroups were compared. RESULTS: Aneurysmal SAH occurred most often from 6am to 12pm (p<0.001); this correlation was not found in naSAH or PMH subgroups. Demographic analysis demonstrated predominance of female gender (p=0.008) and smoking (p=0.002) in aSAH, with predominance of hypercholesterolemia in naSAH (p=0.033). Atmospheric pressure, correlated with aSAH in the main county referral area, where we had detailed weather data (p<0.05); however, there was no weather correlation in the entire referral region taken together. Multivariate analysis supported a statistical difference only in smoking status between aSAH and naSAH groups (p=0.0159). CONCLUSION: Statistical differences in gender, smoking status, and history of hypercholesterolemia support a clinical distinction between aSAH and naSAH. Furthermore, circadian patterning of aSAH is not reproduced in naSAH, supporting pathophysiologic differences. Only smoking status provides a robust difference in aSAH and naSAH groups. Our data prompt further investigation into the relationship between aSAH and atmospheric pressure.