Daisuke Wajima

Neuroprotection with intraventricular brain-derived neurotrophic factor in rat venous occlusion model.

BACKGROUND:The increasing number of neurosurgical procedures for elderly patients and the development of skull base neurosurgery have increased interest in cerebral venous injury that might occur in a neurosurgical setting. Brain-derived neurotrophic factor (BDNF) may have neuroprotective effects against cerebral venous ischemia. OBJECTIVE:To investigate the intraventricular effects of BDNF infusion on infarct size, suppression of apoptosis, and regional cerebral blood flow (rCBF) in cerebral venous ischemic lesions in a rat 2-vein occlusion model. METHODS:Thirty-three male Wistar rats were randomly divided into BDNF-treated and vehicle control groups; each group was further randomly divided into 2-day and 7-day postocclusion groups. BDNF (2.1 μg/day) or vehicle was delivered continuously via intraventricular infusion pumps. Two adjacent contralateral cortical veins were then photochemically occluded. Two and 7 days after occlusion, we histologically measured ratios of infarct volume to contralateral hemisphere volume and counted (2-day group) terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive apoptotic cells in the penumbra. rCBF was measured via full-field laser perfusion imaging. RESULTS:The mean infarct volume after venous occlusion was significantly smaller in BDNF-treated rats than in controls at 2 days (1.49 ± 1.44% vs 3.66 ± 1.51%; P < .05) and 7 days (0.93 ± 0.47% vs 1.69 ± 0.58%; P < .05). Two days after occlusion, there were significantly fewer TUNEL-positive apoptotic cells in the BDNF-treated rats (17.0 ± 15.1) than in the controls (39.0 ± 19.6; P < .05). There were no differences in rCBF. CONCLUSION:After 2-vein occlusion, continuous intraventricular administration of BDNF protected the cerebral cortex against apoptosis and reduced infarct size without affecting rCBF.

Enhanced cerebral ischemic lesions after two-vein occlusion in diabetic rats

The two-vein occlusion (2VO) model is known to be useful for ischemic penumbra studies in vivo. It was applied here to examine sequential changes of regional cerebral blood flow (CBF) and cerebral venous infarction in normal (Long-Evans Tokushima Otsuka, LETO) and diabetic (Otsuka Long-Evans Tokushima Fatty, OLETF) rats. The aim of our study was to examine and compare the ischemic pathogenesis related to regional changes in cerebral blood flow (CBF) induced with 2VO in diabetic OLETF and non-diabetic LETO rats. Two cortical veins were occluded photochemically by using rose bengal dye in 10 OLETF and 10 LETO rats. All animals were killed with perfusion fixation at 48 h after 2VO. Bax and Bcl-2 staining was performed along with the terminal deoxynucleotidyl transderase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay to examine the relationship to single-cell death. Smooth muscle actin and Van Giesons elastic staining were done for assessment of thickening of the vessel walls. Not only the volume of cerebral cortex affected by 2VO-induced venous infarction was increased in diabetic OLETF rats, but we also observed significantly reduced CBF at 90 min after 2VO, coupled with increased apoptosis in and around ischemic lesions. Morphologically, OLETF rats demonstrated marked thickening of the walls in the small cerebral vessels with perivascular fibrosis, indicating more severe cerebral microvascular atherosclerotic changes as compared to their non-diabetic LETO counterparts. The OLETF rat thus appears to be an excellent animal model for studying the diabetic enhancement of venous ischemia induced by 2VO.

The neuroprotective effect of diazoxide is mediated by mitochondrial ATP-dependent potassium channels in a rat model of acute subdural hematoma

Acute subdural hematoma (ASDH) results in neuronal death due to mitochondrial dysfunction and a subsequent cascade of apoptotic and necrotic events. We previously demonstrated that mitochondrial ATP-dependent potassium (mitoK(ATP)) channels have a major role in cerebral ischemic preconditioning in vivo and in vitro. However, the role of the mitoK(ATP) channel has not been investigated in the context of ASDH. Thus, the purpose of this study was to determine whether the mitoK(ATP) channel mediates neuroprotection in a rat model of ASDH. Male Wistar rats were subjected to subdural infusion of 400 μL autologous venous blood. The rats were assigned to four experimental groups pretreated intraventricularly 15 minutes before ASDH with (1) vehicle (n=10); (2) the mitoK(ATP) channel agonist diazoxide (n=9); (3) diazoxide plus the selective mitoK(ATP) channel antagonist 5-hydroxydecanoate (5-HD) (n=6); or (4) 5-HD alone (n=6). Infarct volume was assessed at 4 days after ASDH. Brain edema formation was also measured. Pretreatment with diazoxide significantly reduced infarct volume and brain edema formation after ASDH. However, the effects of diazoxide were abolished by co-treatment with 5-HD. 5-HD alone increased infarct volume. These data suggest that the mitoK(ATP) channel is an important mediator of the neuroprotective effects of cerebral preconditioning in a rat model of ASDH.

Neuroprotective effect of suppression of astrocytic activation by arundic acid on brain injuries in rats with acute subdural hematomas

Acute subdural hematoma (ASDH) can cause massive ischemic cerebral blood flow (CBF) underneath the hematoma, but early surgical evacuation of the mass reduces mortality. The aim of this study was to evaluate whether arundic acid improves the secondary ischemic damage induced by ASDH. Our results confirmed that arundic acid decreases the expression of S100 protein produced by activated astrocytes around ischemic lesions due to cytotoxic edema after ASDH as well as reducing infarction volumes and numbers of apoptotic cells around the ischemic lesions. In this study, we also evaluate the relationship of brain edema and the expression of Aquaporin 4 (AQP4) in an ASDH model. The expression of AQP4 was decreased in the acute phase after ASDH. Cytotoxic edema, assumed to be the main cause of ASDH, could also cause ischemic lesions around the edema area. Arundic acid decreased the infarction volume and number of apoptotic cells via suppression of S100 protein expression in ischemic lesions without changing the expression of AQP4.

Cilostazol minimizes venous ischemic injury in diabetic and normal rats

We evaluated the effects of cilostazol on venous infarction produced by a photothrombotic two-vein occlusion (2VO) model in diabetic and control rats. The cerebral blood flow (CBF) between the occluded veins was measured by laser Doppler flowmetry for 4 hours after 2VO. Infarct size and immunohistochemistry were evaluated 24, 48, 96, and 168 hours after 2VO. Cilostazol was administered 1 hour after 2VO, and thereafter at a continuous oral dose of 60 mg/kg per day. Cilostazol reduced the infarct size, and the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive apoptotic and B-cell lymphoma 2-associated X protein (Bax)-positive cells, and improved the CBF in control rats. In diabetic rats, cilostazol reduced the infarct size, and the number of TUNEL-positive apoptotic and Bax-positive cells, 96 and 168 hours after 2VO, but did not improve the CBF 4 hours after 2VO. Cilostazol increased the number of B-cell lymphoma 2 (Bcl-2)-positive cells in both strains 48, 96, and 168 hours after 2VO, but did not improve vessel wall thickness or collagen deposits. Cilostazol appeared to limit venous infarcts by improving the penumbral CBF in nondiabetic rats, and inhibited pro-apoptotic changes through Bcl-2 overexpression, without improving the CBF in diabetic rats.

A case of filum terminale arterial venous fistula needed a long arterial access for trans-arterial shunt obliteration

A 78-year-old man was referred to our institution with a predominantly progressive numbness of both legs, and bladder dysfunction with urinary retention. He was diagnosed as the symptomatic arteriovenous fistula of the filum terminale (AVFFT). A trans-arterial embolization (TAE) of the arteriovenous shunt was planned for his symptomatic AVFFT. The long distance between the origin of the radiculo meningeal artery (Th8) and the site of the fistula (S1) resulted in the first TAE having a feeder occlusion. The length of accessible feeder in the first TAE was the longest (about 40 cm) as the past reports of the endovascular therapy. However, complete shunt occlusion was accomplished at a second session two weeks after the initial TAE because a more accessible feeder was developed by the initial feeder occlusion.

Nickel-associated delayed multiple white matter lesions after stent-assisted coil embolization of intracranial unruptured aneurysm

Metal-induced encephalopathy after stent-assisted coil embolization is extremely rare. The present report describes two patients who presented with symptomatic intracranial parenchymal edematous lesions after stent-assisted coil embolization. A 64-year-old woman underwent stent-assisted coil embolization for a left internal carotid artery aneurysm; 21 days after the procedure she presented with right hand weakness and MRI revealed multifocal white matter lesions. Another woman aged 52 years underwent stent-assisted coil embolization for right vertebral artery aneurysm; 18 days after the procedure she presented with left-sided sensory disturbance and MRI demonstrated multiple white matter lesions. Treatment in both cases resulted in improvement of these lesions after steroid pulse therapy, and the patients had no associated morbidity 4 months after the procedures. Clinicians should monitor for neurologic symptoms and postoperative delayed radiologic parenchymal edematous changes associated with the metal allergic reaction after nitinol stent-assisted coil embolization.

Relationship Between Clinical Features and T2-Weighted Magnetic Resonance Images in Symptomatic Rathke Cleft Cysts

BACKGROUND It is not known when surgery is appropriate for the treatment for incidental Rathke cleft cysts because knowledge of their natural history is lacking. In this study, we sought to determine whether symptomatic Rathke cleft cysts could be distinguished by their signal intensities in magnetic resonance (MR) images. We analyzed the relationship between these signal intensities and clinical manifestations of the cysts and their patterns of expansion. METHODS MR signal intensities on T1-weighted (T1W) and T2-weighted (T2W) images for 52 cases were categorized into 3 types. Type 1 (20 cases) showed low signal intensities on T1W images and hyperintensity on T2W images. Type 2 (10 cases) showed hyperintensity on both T1W and T2W images. Type 3 (22 cases) showed hypointensity on T2W images. RESULTS A significantly higher proportion of patients with type 1 signal intensities had large cysts compressing their third ventricle than patients with the other 2 types of signal intensities. Patients with type 1 signal intensities also frequently had visual disturbances. Anterior pituitary dysfunction was observed more often in patients with type 2 or 3 signal intensities than in patients with type 1 intensities. CONCLUSIONS We conclude that Rathke cleft cysts that show an MR signal intensity similar to that of cerebrospinal fluid grow slowly and are frequently diagnosed as cysts associated with visual disturbance when they become large. It may be possible to predict the clinical progression of Rathke cleft cysts by assessing MR signal intensities.

Risk of brain herniation after craniotomy with lumbar spinal drainage: a propensity score analysis

OBJECTIVELumbar spinal drainage (LSD) during neurosurgery can have an important effect by facilitating a smooth procedure when needed. However, LSD is quite invasive, and the pathology of brain herniation associated with LSD has become known recently. The objective of this study was to determine the risk of postoperative brain herniation after craniotomy with LSD in neurosurgery overall.METHODSIncluded were 239 patients who underwent craniotomy with LSD for various types of neurological diseases between January 2007 and December 2016. The authors performed propensity score matching to establish a proper control group taken from among 1424 patients who underwent craniotomy and met the inclusion criteria during the same period. The incidences of postoperative brain herniation between the patients who underwent craniotomy with LSD (group A, n = 239) and the matched patients who underwent craniotomy without LSD (group B, n = 239) were compared.RESULTSBrain herniation was observed in 24 patients in group A and 8 patients in group B (OR 3.21, 95% CI 1.36-8.46, p = 0.005), but the rate of favorable outcomes was higher in group A (OR 1.79, 95% CI 1.18-2.76, p = 0.005). Of the 24 patients, 18 had uncal herniation, 5 had central herniation, and 1 had uncal and subfalcine herniation; 8 patients with other than subarachnoid hemorrhage were included. Significant differences in the rates of deep approach (OR 5.12, 95% CI 1.8-14.5, p = 0.002) and temporal craniotomy (OR 10.2, 95% CI 2.3-44.8, p = 0.002) were found between the 2 subgroups (those with and those without herniation) in group A. In 5 patients, brain herniation proceeded even after external decompression (ED). Cox regression analysis revealed that the risk of brain herniation related to LSD increased with ED (hazard ratio 3.326, 95% CI 1.491-7.422, p < 0.001). Among all 1424 patients, ED resulted in progression or deterioration of brain herniation more frequently in those who underwent LSD than it did in those who did not undergo LSD (OR 9.127, 95% CI 1.82-62.1, p = 0.004).CONCLUSIONSBrain herniation downward to the tentorial hiatus is more likely to occur after craniotomy with LSD than after craniotomy without LSD. Using a deep approach and craniotomy involving the temporal areas are risk factors for brain herniation related to LSD. Additional ED would aggravate brain herniation after LSD. The risk of brain herniation after placement of a lumbar spinal drain during neurosurgery must be considered even when LSD is essential.

Successful Coil Embolization of Pediatric Carotid Cavernous Fistula Due to Ruptured Posttraumatic Giant Internal Carotid Artery Aneurysm

BACKGROUND The goal of the treatment of direct carotid cavernous fistula (CCF) is to occlude the arteriovenous shunt and to preserve the patency of the concerned internal carotid artery. However, for the ipsilateral posttraumatic fragile cerebrum, coil embolization plus parent artery occlusion for the high-flow direct CCF is better for the prevention of hyperperfusion syndrome and intracranial hemorrhage. We experienced such a case and managed it successfully. CASE DESCRIPTION A 6-year-old boy had severe head trauma caused by being hit by a car. He was transferred to our department and diagnosed as having left acute subdural hematoma and acute brain swelling. Emergent evacuation of hematoma and external decompression were performed. He was treated for severe brain swelling in the intensive care unit for 2 months. Cranioplasty was performed 3 months after the injury. His right hemiparesis and aphasia persisted, so he was transferred to a rehabilitation hospital. However, 2 years after the head injury, he was referred to our department because of abducens nerve palsy. He was diagnosed as having a symptomatic posttraumatic direct CCF, which was caused by a ruptured left cavernous giant internal carotid artery aneurysm. The direct CCF was treated with coil embolization of the giant aneurysm and parent artery occlusion. CONCLUSIONS Coil embolization of the aneurysm and parent artery occlusion for the posttraumatic direct CCF was a good option to manage the abducens nerve palsy and to prevent postoperative hyperperfusion.