Disease relevance of Brain Injuries

• Modified peptides, such as acetyl-tyrosinyl-valyl-alanyl-aspartyl-chloro-methylketone (Ac-YVAD-cmk), that specifically inhibit proteases of the caspase family effectively block apoptosis in a plethora of experimental paradigms, such as growth factor withdrawal, excitotoxicity, axotomy, cerebral ischemia and brain trauma [1].
• Following neonatal H-I brain injury in mice (a model of cerebral palsy), there was evidence of apoptotic changes (neuronal caspase-3 activation), as well as accumulation of clusterin in dying neurons [2].
• Thus, excitatory amino acids contribute to delayed tissue damage after brain trauma; NMDA antagonists may be of benefit in treating acute head injury [3].
• Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months: results from the trial of indomethacin prophylaxis in preterms [4].
• Recent studies have highlighted a crucial role for IL-18 in mediating neuroinflammation and neurodegeneration in the CNS under pathological conditions, such as bacterial and viral infection, autoimmune demyelinating disease, and hypoxic-ischemic, hyperoxic and traumatic brain injuries [5].

Psychiatry related information on Brain Injuries

• Plaques composed of amyloid beta (Abeta) have been found within days following brain trauma in humans, similar to the hallmark plaque pathology of Alzheimer's disease (AD) [6].
• There was also a significant diagnosis-by-allele interaction on measures of response latency (Continuous Performance Test): the subjects with mild traumatic brain injury and the T allele had the worst performance [7].
• Among the issues covered are steroid-induced sedation and epileptogenicity, excitatory steroids, stress and epilepsy, GABA and respiratory functions, asymmetric brain injury, and psychopathology and stress [8].
• The main focus of this article is on movement disorders, neuromuscular diseases, multiple sclerosis, dementia, cerebrovascular diseases, head and brain trauma, pain and epilepsy [9].
• METHODS: B-FABP and H-FABP were measured immunochemically in autopsy samples of the brain (n = 6) and in serum samples from (a) patients with mild traumatic brain injury (MTBI; n = 130) and (b) depressed patients undergoing bilateral electroconvulsive therapy (ECT; n = 14) [10].

High impact information on Brain Injuries

• The glucose-transporter protein and glucopenic brain injury [11].
• An EP1 receptor inhibitor reduces brain injury when administered 6 hours after MCA occlusion, suggesting that EP1 receptor inhibition may be a viable therapeutic option in ischemic stroke [12].
• In mice overexpressing human UCP-2, brain damage was diminished after experimental stroke and traumatic brain injury, and neurological recovery was enhanced [13].
• Hence it is possible that tPA upregulates MMPs in the brain, and that subsequent matrix degradation causes brain injury [14].
• Clusterin contributes to caspase-3-independent brain injury following neonatal hypoxia-ischemia [2].

Chemical compound and disease context of Brain Injuries

• We found that in a rat model of acute brain injury, the beta-receptor antagonist propranolol prevented the increase of interleukin-10 plasma levels [15].
• Drugs that target TNF signaling pathways may prove beneficial in treating stroke and traumatic brain injury [16].
• Moreover, acute brain injury increases the levels of excitotoxic amino acids (such as glutamate), which also produce ROS, thereby promoting parenchymatous destruction [17].
• The role of excitatory amino acids and NMDA receptors in traumatic brain injury [3].
• The effect of ethanol on sprouting axons suggests that it may inhibit recovery of function after brain injury [18].

Biological context of Brain Injuries

• After a severe episode of ischemia, traumatic brain injury (TBI) or epilepsy, it is typical to find necrotic cell death within the injury core [19].
• This may underlie the important influence of APOE genotype on brain injury and disease [20].
• Apoptotic cells and, even more so, necrotic cells in acute brain injury are potential sources for autoantigen presentation that may stimulate autoimmune responses [21].
• This study unequivocally demonstrates coordinate up-regulation and trafficking of FGF-2 and full-length FGFR1 to the nucleus of reactive astrocytes in an in vivo model of brain injury, thereby implicating a role in nuclear activity for these molecules [22].
• The effect of a moderate level of fluid-percussion brain injury on acetylcholine-induced cerebral arteriolar vasodilation was examined for 12 hours after trauma in anesthetized cats equipped with cranial windows [23].

Anatomical context of Brain Injuries

• These data suggest that the SCF/c-kit pathway is involved in the migration of NSPCs to sites of brain injury and that SCF may prove useful for inducing progenitor cell recruitment to specific areas of the CNS for cell-based therapeutic strategies [24].
• FGF-2 regulation of neurogenesis in adult hippocampus after brain injury [25].
• Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury [26].
• We demonstrate that COX-2-deficient mice have a significant reduction in the brain injury produced by occlusion of the middle cerebral artery [27].
• Anesthetized cats equipped with a cranial window for the observation of the pial microcirculation were subjected to concussive brain injury using a fluid-percussion device following administration of cyclooxygenase inhibitors (indomethacin or AHR-5850) or the vehicle for the solution of these agents (NaCl or Na2CO3 solution) [28].

Gene context of Brain Injuries

• Clusterin-deficient mice had 50% less brain injury following neonatal H-I [2].
• Our findings suggest a role for APP in axonal outgrowth after traumatic brain injury [29].
• The cytokine erythropoietin (EPO) possesses potent neuroprotective activity against a variety of potential brain injuries, including transient ischemia and reperfusion [30].
• This study indicates that the MEK1/ERK pathway contributes to brain injury during focal cerebral ischemia and that PD98059, a MEK1-specific antagonist, is a potent neuroprotective agent [31].
• Estrogen receptor alpha, not beta, is a critical link in estradiol-mediated protection against brain injury [32].

Analytical, diagnostic and therapeutic context of Brain Injuries

• Using a mouse model of traumatic brain injury and quantitative autoradiography of the activity-dependent NMDA receptor antagonist MK801, we show that hyperactivation of glutamate NMDA receptors after injury is short-lived (<1 h) and is followed by a profound and long-lasting (> or =7 days) loss of function [33].
• To investigate the potential role of drug therapy in preventing or exacerbating seizure-related brain injury in the prepubescent brain, we administered kainic acid to rats at postnatal day 35 [34].
• To investigate the fate of ICAM-5 during focal brain injury, we induced hypoxia-ischemia (HI) damage in adult mice by right common carotid artery ligation followed by hypoxia [35].
• Intraperitoneal injection of recombinant human IL-18-binding protein, a specific inhibitor of IL-18, attenuated hyperoxic brain injury [36].
• In summary, BAG1 displays potent neuroprotective activity in vivo against stroke, and therefore represents an interesting target for developing new therapeutic strategies including gene therapy and small-molecule drugs for reducing brain injury during cerebral ischemia and neurodegenerative diseases [37].

References