Modafinil attenuates the neuroinflammatory response after experimental traumatic brain injury.

BACKGROUND: Modafinil has been proven to exert anti-inflammatory, anti-oxidative and neuroprotective effects on numerous neurological disorders. However, its effects after traumatic brain injury (TBI) have not been yet explored. The aim of this study was to explore if Modafinil can attenuate the neuroinflammatory phase of TBI and clarify the possible underlying mechanisms. METHODS: A weight drop model was used to induce experimental TBI on 30 Wistar albino rats. The treatment group received Modafinil on the day of the trauma and the following 5 days. Garcia Test was used to assess for neurological status and histopathological examination along with biochemical analysis of NSE, S-100B, CASP3, and TBARS levels were performed. RESULTS: Rats treated with Modafinil after the trauma had a statistically significant higher Garcia Test Score (P<0.001) and presented with increased evidence of anti-inflammatory and neuroprotective effect (P<0.05, P=0.005). Decreased levels of all biochemical parameters with NSE, CASP3, and TBARS having statistical significance was observed (P<0.05). CONCLUSIONS: The findings of this paper support the notion that a psychoactive drug Modafinil, traditionally used for sleep disorders and also known as a cognitive enhancer may prove beneficial in decreasing mortality and morbidity after TBI through anti-inflammatory, anti-oxidative and neuroprotective effects.

Spinal meningiomas: 61 cases with predictors of early postoperative surgical outcomes.

BACKGROUND: Spinal meningiomas are benign, well-circumscribed and slowly-growing intradural tumors that compress the spinal cord. Hereby, a retrospective review of 61 spinal meningioma cases evaluated in terms of demographic, clinical, pathological and radiological features to predict the early postoperative functional outcomes. METHODS: Patients' records and MRI images of all the histologically confirmed spinal meningioma cases that underwent surgical resection at two university hospitals from January 2005 to June 2016 were retrospectively reviewed. Demographic data, clinical findings, radiological features and pathology reports were reviewed. Univariate and multivariate logistic regression analyses were used to evaluate the impact of each factor on the early 3-month post-surgical functional outcome. A receiver operating characteristic (ROC) curve was used to predict the power of the model. RESULTS: Sixty-one cases of spinal meningiomas were operated: 13 males (21%) and 48 females (79%). Mean age was 60.5 years and ranged from 24 to 92 years. Patients presented with back pain (57%), motor deficits (47.5%), sensory deficits (18%) and sphincteric dysfunction (11.5%). One case (1.6%) showed an additional extradural growth. There were 40 thoracic, nine cervical, five cervicothoracic, five thoracolumbar, and two lumbar cases. Only four cases (6.6%) showed atypical pathological features (WHO grade II). At 3-month follow-up, 46 patients (75.4%) had either functionally improved or remained stable. Fifteen patients (24.6%) had "worse" functional outcome. Three variables showed statistically significant odds ratio for improved outcomes (OR): pre-surgical motor deficit (OR=5; P=0.005); presurgical sensory disturbance (OR=3.5; P=0.026); pre-surgical myelopathy (OR=3.5; P=0.026). Multivariate analysis showed increased OR for cross-sectional ratio, pre-surgical myelopathy, pre-surgical radiculopathy and non-cervical location of tumor (1.59, 3.46, 3.2, 1.63/3.56, respectively). Although none has reached statistical significance (P>0.05), the receiver operating characteristic (ROC) curve showed an area under the curve (AUC) of 0.74. CONCLUSIONS: The independent predictors of the early postoperative functional outcomes of spinal meningioma resections may include pre-surgical motor deficit, sensory deficit and myelopathy.

New Histopathologic Evidence for the Parasympathetic Innervation of the Kidney and the Mechanism of Hypertension Following Subarachnoid Hemorrhage.

BACKGROUND: The Cushing response was first described in 1901. One of its components is elevated systemic blood pressure secondary to raised intracranial pressure. However, controversy still exists in its pathophysiologic mechanism. Hypertension is attributed to sympathetic overactivity and vagotomy increased renal-based hypertension. However, the role of the parasympathetic system in hypertension has not been investigated. This subject was investigated following subarachnoid hemorrhage (SAH). METHODS: A total of 24 rabbits were used: control group (n = 5), SHAM group (n = 5), and an SAH group (n = 14; bolus injection of blood into the cisterna magna). Blood pressures were examined before, during, and after the experiment. After 3 weeks, animals were decapitated under general anesthesia. Vagal nodose ganglion, axonal degeneration, and renal artery vasospasm (RAV) indexes of all animals were determined histopathologically. RESULTS: Significant degenerative changes were detected in the vagal axons and nodose ganglia following SAH in animals with severe hypertension. The mean degenerated neuron density of nodose ganglions, vasospasm index (VSI) values of renal arteries of control, SHAM, and study groups were estimated as 9.0 ±â€Š2.0 mm, 1.87 ±â€Š0.19; 65.0 ±â€Š12.0 mm, 1.91 ±â€Š0.34; and 986.0 ±â€Š112.0 mm, 2.32 ±â€Š0.89, consecutively. Blood pressure was measured as 94.0 ±â€Š10.0 mmHg in control group, 102.0 ±â€Š12.0 mmHg in SHAM; 112.0 ±â€Š14.0 mmHg in middle (n = 9); and >122.0 ±â€Š10.0 mmHg in severe RAV-developed animals (n = 5). Differences VSI values and blood pressure between groups were statistically significant (P < 0.05). CONCLUSION: The degeneration of vagal nodose ganglion has an important role in RAV and the development of RAV and hypertension following SAH.

New Evidence for Causal Central Mechanism of Hyperglycemia in Subarachnoid Hemorrhage Secondary to Ischemic Degenerative Disruption of Circuitry Among Insular Cortex, Nodose Ganglion, and Pancreas: Experimental Study.

INTRODUCTION: Although hyperglycemia is a serious complication of subarachnoid hemorrhage, its pathophysiologic mechanism based on neural circuitry has not been known. MATERIALS AND METHODS: Twenty-five rabbits were divided into 4 groups, with 5 in the control group. The SHAM and study groups received 1 mL saline and 1 mL autologous arterial blood into the sylvian cisterna, respectively. Blood glucose values (BGVs) of all animals were recorded 3 times weekly. After 2 weeks, animals were decapitated. BGVs, the number of normal and degenerated neuron densities (DNDs) of insular cortex (IC), and nodose ganglia, degenerated islands of Reil's surfaces values, were estimated by stereologically and analyzed statistically. RESULTS: The mean blood glucose values were measured as 101 ± 10 mg/dL in the control group (n = 5), 114 ± 11 mg/dL in the SHAM group (n = 5), and 137 ± 12 mg/dL in the subarachnoid hemorrhage (SAH) group (n = 15). The DND of the nodose ganglion was 10 ± 3/mm3 in the control group, while it was 45 ± 7/mm3 in the SHAM group and 1688 ± 191/mm3 in the SAH group. The DND of the IC was 65 ± 12/mm3 in the control group, 689 ± 112/mm3 in the SHAM group, and 3709 ± 643/mm3 in the SAH group. In addition, the proportion of degenerated surface areas in the islet of Langerhans was 0.3% in the control group, 6% in the SHAM group, and 28% in the SAH group. CONCLUSION: There is an important linear relationship among the blood glucose levels, DND of the IC, and nodose ganglia and degenerated surface areas of IL following experimentally induced sylvian SAH.

A New Determinant of Poor Outcome After Spontaneous Subarachnoid Hemorrhage: Blood pH and the Disruption of Glossopharyngeal Nerve-Carotid Body Network: First Experimental Study.

OBJECTIVE: The chemoreceptor network, consisting of the glossopharyngeal nerve and carotid body (GPN-CB), is essential for the regulation of blood pH. Its ischemic insults after subarachnoid hemorrhage (SAH), which may contribute to acidosis, have not been investigated. METHODS: Twenty-three hybrid rabbits were used. They were divided into 3 groups: 5 as a control group, 5 as a sham group, and the remaining 13 as the study group. Injections included 1 cm3 serum saline and 1 cm3 autolog arterial blood into the cisterna magna in the sham and study group, respectively. Blood pH values of all animals were recorded. After 2 weeks, animals were euthanized. The number of normal and degenerated neurons of the carotid bodies (CBs) was counted by stereologic methods and analyzed statistically. RESULTS: Two of 13 rabbits died within the second week. The mean blood pH values were measured as 7.35 ± 0.07 in the control group (n = 5), 7.33 ± 0.06 in the sham group (n = 5), 7.29 ± 0.05 in rabbits with slight acidosis (n = 6), and 7.23 ± 0.02 in rabbits with prominent acidosis (n = 7). In the control group, the average normal neuronal density of the CBs was 6432 ± 790/mm3 and the degenerated neuron density was 11 ± 3/mm3, whereas the degenerated neuronal density in CBs was 35 ± 8/mm3 in the sham group and 1034 ± 112/mm3 in the slight acidosis-developed group (n = 6; P < 0.05). Conversely, degenerated neuron density of CBs was 2134 ± 251/mm3 in the prominent acidosis-developed animals (n = 7; P < 0.005). Interestingly, in the rabbits who died, the degenerated neuron density of the CB was 3160 ± 840/mm3. CONCLUSION: An inverse relationship between neurodegeneration in the CB and pH values secondary to the disruption of the GPN-CB network after SAH was found, which may contribute to developing acidosis.

Uncovering a New Cause of Obstructive Hydrocephalus Following Subarachnoid Hemorrhage: Choroidal Artery Vasospasm-Related Ependymal Cell Degeneration and Aqueductal Stenosis-First Experimental Study.

BACKGROUND: Hydrocephalus is a serious complication of subarachnoid hemorrhage (SAH). Obstruction of the cerebral aqueduct may cause hydrocephalus after SAH. Although various etiologic theories have been put forward, choroidal artery vasospasm-related ependymal desquamation and subependymal basal membrane rupture as mechanisms of aqueductal stenosis have not been suggested in the literature. METHODS: This study was conducted on 26 hybrid rabbits. Five rabbits were placed in a control group, 5 were placed in a sham group, and the remaining rabbits (n = 16) were placed in the SAH group. In the first 2 weeks, 5 animals in the SAH group died. The other 21 animals were decapitated after the 4-week follow-up period. Choroidal artery changes resulting from vasospasm, aqueduct volume, ependymal cell density, and Evans index values of brain ventricles were obtained and compared statistically. RESULTS: Mean aqueduct volume was 1.137 mm(3) ± 0.096, normal ependymal cell density was 4560/mm(2) ± 745, and Evans index was 0.32 ± 0.05 in control animals (n = 5); these values were 1.247 mm(3) ± 0.112, 3568/mm(2) ± 612, and 0.34 ± 0.15 in sham animals (n = 5); 1.676 mm(3) ± 0.123, 2923/mm(2) ± 591, and 0.43 ± 0.09 in animals without aqueductal stenosis (n = 5); and 0.650 mm(3) ± 0.011, 1234/mm(2) ± 498, and 0.60 ± 0.18 in animals with severe aqueductal stenosis (n = 6). The choroidal vasospasm index values were 1.160 ± 0.040 in the control group, 1.150 ± 0.175 in the sham group, 1.760 ± 0.125 in the nonstenotic group, and 2.262 ± 0.160 in the stenotic group. Aqueduct volumes, ependymal cell densities, Evans index, and choroidal artery vasospasm index values were statistically significantly different between groups (P < 0.05). CONCLUSIONS: Ependymal cell desquamation and subependymal basal membrane destruction related to choroidal artery vasospasm may lead to aqueductal stenosis and hydrocephalus after SAH.