Ulas Cikla

ERα Signaling Is Required for TrkB-Mediated Hippocampal Neuroprotection in Female Neonatal Mice after Hypoxic Ischemic Encephalopathy(1,2,3).

Abstract Male neonate brains are more susceptible to the effects of perinatal asphyxia resulting in hypoxia and ischemia (HI)-related brain injury. The relative resistance of female neonatal brains to adverse consequences of HI suggests that there are sex-specific mechanisms that afford females greater neuroprotection and/or facilitates recovery post-HI. We hypothesized that HI preferentially induces estrogen receptor α (ERα) expression in female neonatal hippocampi and that ERα is coupled to Src family kinase (SFK) activation that in turn augments phosphorylation of the TrkB and thereby results in decreased apoptosis. After inducing the Vannucci’s HI model on P9 (C57BL/6J) mice, female and male ERα wild-type (ERα+/+) or ERα null mutant (ERα−/−) mice received vehicle control or the selective TrkB agonist 7,8-dihydroxyflavone (7,8-DHF). Hippocampi were collected for analysis of mRNA of ERα and BDNF, protein levels of ERα, p-TrkB, p-src, and cleaved caspase 3 (c-caspase-3) post-HI. Our results demonstrate that: (1) HI differentially induces ERα expression in the hippocampus of the female versus male neonate, (2) src and TrkB phosphorylation post-HI is greater in females than in males after 7,8-DHF therapy, (3) src and TrkB phosphorylation post-HI depend on the presence of ERα, and (4) TrkB agonist therapy decreases the c-caspase-3 only in ERα+/+ female mice hippocampus. Together, these observations provide evidence that female-specific induction of ERα expression confers neuroprotection with TrkB agonist therapy via SFK activation and account for improved functional outcomes in female neonates post-HI.

Suppression of microglia activation after hypoxia-ischemia results in age-dependent improvements in neurologic injury.

We previously found increased microglial proliferation and pro-inflammatory cytokine release in infant mice compared to juvenile mice after hypoxia-ischemia (HI). The aim of the current study was to assess for differences in the effect of microglial suppression on HI-induced brain injury in infant and juvenile mice. HI was induced in neonatal (P9) and juvenile (P30) mice and minocycline or vehicle was administered at 2h and 24h post-HI. P9 minocycline-treated mice demonstrated early but transient improvements in neurologic injury, while P30 minocycline-treated mice demonstrated sustained improvements in cerebral atrophy and Morris Water Maze performance at 60days post-HI.

Fatal Ruptured Blood Blister-like Aneurysm of Middle Cerebral Artery Associated with Ehlers-Danlos Syndrome Type VIII (Periodontitis Type).

Objective To illustrate a unique instance of Ehlers-Danlos syndrome type VIII (EDS VIII) with blood blister–like aneurysm of the middle cerebral artery. Design This is a single patient case report. Setting University of Wisconsin-Madison Hospital. Participants A 42-year-old woman with diagnosis of EDS VIII presented with a sudden onset severe headache and altered mental status. She was diagnosed with Hunt and Hess grade IV subarachnoid hemorrhage. Angiography demonstrated a blood blister–like aneurysm of the left middle cerebral artery. After an unsuccessful coiling attempt in another facility, the patient was operated on with the intention to perform extracranial to intracranial bypass and trapping of the diseased segment of the artery. Results The patients neurologic condition remained poor after surgery. On postoperative day 2, her neurologic examination unchanged, and care was withdrawn per the familys request. Conclusions Individuals with EDS VIII may be at risk for catastrophic vascular events.

Microsurgical anatomy of the denticulate ligaments and their relationship with the axilla of the spinal nerve roots

The denticulate ligaments (DL), 20 or 21 pairs of meningeal extensions, spread from the lateral aspect of the spinal cord to the internal aspect of the spinal dura mater. The aim of this study is to define the specific relationship of the DL with adjacent axilla of the spinal nerve roots and to investigate the anatomical features of the DLs and their variations. The topographical anatomy of the DLs and their relationships with the adjacent axilla of the spinal nerve roots was examined on 16 formalin‐fixed adult cadaveric spinal cords. The distances from the dural attachment of the DL to the axilla of the superior and inferior spinal nerve roots were measured bilaterally at every spinal level. Also the distances from the dural attachment of the DL to the lateral aspect of the spinal cord were measured bilaterally. Cervical DLs showed a triangular shape, while in the thoracic segment the ligament changes the shape to “Y.” Also the most caudal DL was identified to be at the L1–2 level. Our study revealed that the distances from the dural attachment of the DL to the superior and inferior spinal nerve root axilla were different at the cervical, upper thoracic and the lower thoracic segments. Both distances to the superior and inferior spinal nerve root axilla were shown to increase from cervical to lower thoracic segments. This study provides a detailed anatomy of the DLs and their relationship with the adjacent spinal nerve root axilla. Clin. Anat. 27:733–737, 2014.

A stepwise illustration of the retrosigmoid approach for resection of a cerebellopontine meningioma.

The retrosigmoid approach is a work-horse approach to the cerebellopontine angle (CPA), providing access from the foremen magnum to the tentorium. Indications for this approach are variable such as resection of meningiomas, acoustic neuromas and epidermoid tumors, treatment of vascular lesions of vertebrobasilar system, vascular decompression of cranial nerves (V, VII, IX, X), cranial nerve neurectomies, and intrinsic lesions of the cerebellum and brainstem. In this video, we demonstrate the use of retrosigmoid craniotomy for resection of a large CPA meningioma, delineating all steps including positioning, mapping. The video can be found here: http://youtu.be/kISkYS16Brk .

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.

Microsurgical resection of tumors of the lateral and third ventricles: operative corridors for difficult-to-reach lesions

Tumors of the lateral and third ventricles are cradled on all sides by vital vascular and eloquent neural structures. Microsurgical resection, which always requires attentive planning, plays a critical role in the contemporary management of these lesions. This article provides an overview of the open microsurgical approaches to the region highlighting key clinical perspectives.

Glioblastoma multiforme in Klippel-Trenaunay-Weber syndrome: a case report

IntroductionKlippel-Trenaunay-Weber syndrome (KTWS) is a rare syndrome in which patients usually present with cutaneous hemangiomas, venous varicosities, and bone and soft tissue hypertrophy of the affected limb. Intracranial lesions in patients with KTWS are extremely rare, and are generally reported as single cases in the literature. We describe a rare case, where a patient with KTWS was found with a hemorrhagic grade IV astrocytoma. Although central nervous system abnormalities such as intracranial aneurysms and cerebral and spinal cord cavernomas have been described in patients with KTWS, to the best of our knowledge, this is the first report of an association between glioblastoma multiforme (grade IV astrocytoma) and KTWS in the English-language medical literature.Case presentationA 61-year-old white Caucasian man with a history of KTWS presented with seizures. Left upper and lower extremity hypertrophy, left foot, leg and ear gigantism and left-sided abdominal capillary hemangiomas were noted in the physical examination. Cranial computed tomography (CT) and magnetic resonance imaging (MRI) were obtained, showing a heterogeneous lesion in the cingulate gyrus, with peripheral and central areas of T1 hyperintensity and layering T2 hypointensity consistent with a hemorrhage. A right parasagittal frontal craniotomy was performed with an interhemispheric approach. We had difficulty controlling the bleeding with bipolar electrocautery during surgery and finally were able to stop the bleeding using surgicel and gelfoam. Postoperative cranial CT and MRI scans showed intraparenchymal hemorrhage centered within the medial right frontal lobe. There was no increase in hematoma size in consecutive CT scans.ConclusionsCo-occurrence of vascular abnormalities with KWTS should be taken into consideration to avoid perilous preoperative and postoperative complications.

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. Clin. Anat. 28:45–51, 2015.

How I do it: treatment of blood blister-like aneurysms of the supraclinoid internal carotid artery by extracranial-to-intracranial bypass and trapping

BackgroundBlood blister-like aneurysms (BBAs) pose a significant challenge to neurosurgeons and neuro-interventionalists. These fragile broad-based aneurysms have a propensity to rupture with minimal manipulation during surgical or endovascular explorations because, unlike saccular aneurysms, they lack all layers of the arterial wall. Aneurysm trapping with extracranial-intracranial (EC-IC) bypass is a safe and durable treatment for BBAs.MethodsWe describe our technique and the guiding principles for surgical bypass and trapping of BBAs of the supraclinoid internal carotid artery (ICA).ConclusionsTreatment of BBAs of the supraclinoid ICA remains difficult. Aneurysm trapping with EC-IC bypass treats BBAs definitively by eliminating the diseased segment of the ICA. We have found the technique and principles described here to be safe and durable in our hands.