Brain injury

Involvement of GMRP1, a novel mediator of Akt pathway, in brain damage after intracerebral hemorrhage

Authors: Zheng M, Zhu H, Gong Y, Wang D, Xie Q, Tang H, Yang Z, Lu B, Chen X, Wang X.

GMRP1, also known as BTBD10, has been reported to inhibit apoptosis of neuronal and islet beta cells via Akt pathway. The present study attempted to investigate whether GMRP1 and its mediated Akt pathway were involved in brain injury of rats after intracerebral hemorrhage (ICH). Rat models of ICH had been established successfully. Western blotting was used to investigate the levels of GMRP1 protein in caudate nuclei tissues of hemorrhagic and contralateral sides at 6 h, day 1, day 3, day 5, day 7 after ICH. Phosphorylation of Akt was determined in caudate nuclei mentioned above. TUNEL assay was used to measure the cell apoptosis. GMRP1 protein levels, as well as phosphorylations of Akt, significantly decreased in caudate nuclei of hemorrhagic side, compared with those of contralateral side at day 1, day 3 after ICH. Enhanced cell apoptosis was observed in hemorrhagic side by TUNEL assay. We presented here evidence that decreased GMRP1-mediated Akt pathway contributed to cell apoptosis in hemorrhagic side, suggesting that GMRP1 played an important role in brain damage after ICH.

Cortical spreading depolarization: An underestimated phenomenon after human brain injury?

Authors: Bapteste L, Marinesco S, Lieutaud T.

BACKGROUND AND PURPOSE: Cortical spreading depolarization waves (CSD) are massive temporary neuronal depolarizations that slowly propagate through cerebral cortex from brain injured tissue. CSD waves cause temporary brain electrical silence, local tissue hemodynamic responses and metabolic increases required for cellular repolarization. Due to this metabolic imbalance in compromised tissue, CSD could participate in the extension of secondary insults after brain injury. From the analysis of the human literature, we aimed at determine the CSD incidences in brain injured patients.
METHODS: Medline(®) research: "cortical spreading depolarization" and "brain injury", and "human" limits from 1980 to 2011.
RESULTS: Ten original studies were found. CSD occurred in more than 50% of patients monitored for CSD after different brain injury (traumatic, subarachnoid haemorrhage, malignant stroke, spontaneous intracranial haemorrhage). When detected, CSD were associated with a significantly worse neurological outcome. To be identified, CSD required specific devices that directly record cortical electrical depression by a multipolar electrode positioned at the cortex surface or by indirect analysis of hemodynamic and metabolic consequences of the CSD.
CONCLUSIONS: When monitoring tools are available, CSD occur in more than 50% of brain injured patients. Today results come from clinical research. Future studies are necessary to determine the impact of CSD detection on care and potential therapeutics aimed at counteracting these adverse events.
Copyright © 2013. Published by Elsevier Masson SAS.

Early brain injury following aneurysmal subarachnoid hemorrhage: emphasis on cellular apoptosis

Authors: Yuksel S, Tosun YB, Cahill J, Solaroglu I.

Subarachnoid hemorrhage (SAH) due to intracranial aneurysm rupture is a complex clinical disease with high mortality and morbidity. Recent studies suggest that early brain injury (EBI) rather than vasospasm might be responsible for morbidity and mortality within 24-72 hours after SAH. The rise in intracranial pressure following SAH causes a significant drop in cerebral perfusion pressure that leads to global cerebral ischemia and initiates the acute injury cascade. Various molecular mechanisms have been shown to involve in the pathophysiology of EBI including cellular apoptosis. In this review, we summarize apoptotic molecular mechanisms involved in the etiology of EBI and its potential as a target for future therapeutic intervention.

Pretransplant Neurological Presentation and Severe Posttransplant Brain Injury in Patients With Acute Liver Failure

Authors: Tan WF, Steadman RH, Farmer DG, Hong JC, Busuttil RW, Apinyachon W, Xia VW.

BACKGROUND: Alterations in the central nervous system in patients with acute liver failure (ALF) present unique challenges in the perioperative period. In this retrospective study, we examined pretransplant neurological presentation and the incidence, clinical presentation, and risk factors associated with severe posttransplant brain injury (BI) in ALF patients undergoing orthotopic liver transplantation (OLT).
METHODS: After institutional review board approval, ALF patients who underwent OLT between 2004 and 2010 at our center were reviewed. Pretransplant neurological presentation and severe posttransplant BI were examined. Risk factors for the latter were identified.
RESULTS: During the study period, 90 (67 adults and 23 children) ALF patients underwent primary OLT. Preoperatively, all patients developed encephalopathy, 6 had seizure activity, 32 had radiological evidence of cerebral edema, and 11 had severe cerebral edema. After OLT, 7 patients developed severe posttransplant BI. Of these 7 patients, 4 had brain death, and 3 had irreversible injury that precluded them from living independently. Severe pretransplant cerebral edema and a higher posttransplant international normalized ratio (odds ratios and 95% confidence intervals: 50.2, 5.8-433.5 and 3.1, 1.1-8.8 , respectively) were risk factors associated with severe posttransplant BI.
CONCLUSIONS: Pretransplant neurological complications were prevalent, and severe posttransplant BI occurred at a rate of 7.8% and was significantly associated with severe pretransplant cerebral edema and postoperative international normalized ratio. Our findings support the use of pretransplant computed tomography. If severe pretransplant cerebral edema is confirmed, efforts should be made to aggressively control intracranial pressure and select a proper donor to minimize the risk of severe posttransplant BI and futile transplantation.

Vascular, electrophysiological, and metabolic consequences of cortical spreading depression in a mouse model of simulated neurosurgical conditions

Authors: Carlson AP, Carter RE, Shuttleworth CW.

OBJECTIVES: Cortical spreading depression (CSD) is a metabolically taxing wave of cellular depolarization that propagates slowly across the brain. Though CSD is known to occur after brain injury in humans, it is unknown if CSD occurs during neurosurgical procedures. This study evaluates CSD in a mouse model of simulated neurosurgical conditions.
METHODS: Mice were intubated and ventilated, maintained at ∼37°C, an arterial line placed to monitor mean arterial pressure and maintain pCO(2) ∼30 mmHg. Mice were given simulated neuroanesthesia (fentanyl, propofol, and isofluorane). Burrholes and craniotomies were made to record the response to cortical bipolar cauterization. Separate sets of experiments (three animals each) examined electrocorticographic (ECoG) activity, optical measures of blood volume and vascular diameters (540 nm absorbance), and autofluorescence attributed to NADH (750 nm, two-photon excitation).
RESULTS: Ipsilateral cauterization invariably resulted in a propagating CSD wave identified by slow DC potential shifts (2.8±0.2 mm/minute, n=6) and suppression of ECoG activity (range 0.5?7.3 minutes, n=10). Each CSD was associated with an initial arteriolar constriction and decreased blood volume, followed by a longer-lasting vasodilation and increased blood volume. Tissue oxygenation, assessed indirectly by NADH imaging, was consistent with demand on oxidative metabolism following each CSD. Repetitive SDs resulted in loss of tissue autofluorescence, suggestive of tissue compromise.
CONCLUSIONS: CSD is consistently elicited by simulated neurosurgical stimuli under simulated intraoperative conditions in mice. These events caused ECoG depression, transient vasoconstriction, and metabolic demand that propagated from the manipulation site. It is likely that CSD occurs during neurosurgery and may contribute to surgical brain injuries otherwise poorly explained.

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