Brain edema leading to an expansion of brain volume has a crucial impact on morbidity and mortality following traumatic brain injury as it increases intracranial pressure, impairs cerebral perfusion and oxygenation, and contributes to additional ischemic injuries. Classically, two major types of traumatic brain edema exist: "vasogenic" and "cytotoxic/cellular". However, the cellular and molecular mechanisms contributing to the development/resolution of traumatic brain edema are poorly understood and no effective drugs can be used now. Aquaporin-4 (AQP4) is a water-channel protein expressed strongly in the brain, predominantly in astrocyte foot processes at the borders between the brain parenchyma and major fluid compartments, including cerebrospinal fluid and blood. This distribution suggests that AQP4 controls water fluxes into and out of the brain parenchyma. In cytotoxic edema, AQP4 deletion slows the rate of water entry into brain, whereas in vasogenic edema, AQP4 deletion reduces the rate of water outflow from brain parenchyma. AQP4 has been proposed as a novel drug target in brain edema. These findings suggest that modulation of AQP4 expression or function may be beneficial in traumatic brain edema.
Animals ; Aquaporin 4 ; analysis ; antagonists & inhibitors ; chemistry ; physiology ; Brain ; metabolism ; Brain Edema ; drug therapy ; etiology ; Brain Injuries ; complications ; Humans ; Mice

Drinking culture has high significance in both China and the world, whether in the entertainment sector or in social occasions; according to the World Health Organization's 2018 Global Alcohol and Health Report, about 3 million people died from excessive drinking in 2016, accounting for 5.3% of the total global deaths that year. Oxidative stress and inflammation are the most common pathological phenomena caused by alcohol abuse (Snyder et al., 2017). Scutellarin, a kind of flavonoid, is one of the main active ingredients extracted from breviscapine. It exerts anti-inflammatory, antioxidant, and vasodilation effects, and has been used to treat cardiovascular diseases and alcoholic liver injury. Although scutellarin can effectively alleviate multi-target organ injury induced by different forms of stimulation, its protective effect on alcoholic brain injury has not been well-defined. Therefore, the present study established an acute alcohol mice brain injury model to explore the effect of scutellarin on acute alcoholic brain injury. The study was carried out based on the targets of oxidative stress and inflammation, which is of great significance for the targeted therapy of clinical alcohol diseases.
Animals ; Apigenin/therapeutic use* ; Brain Injuries/drug therapy* ; Glucuronates/therapeutic use* ; Humans ; Mice ; Oxidative Stress

Animals ; Brain Injuries ; drug therapy ; Gynostemma ; Learning ; drug effects ; Memory ; drug effects ; Phytotherapy ; Saponins ; pharmacology ; therapeutic use

OBJECTIVETo observe cerebral protective effect of muscone (nasal administration) on traumatic brain injury model rats.

METHODSSD rats were divided into the sham-operation group, the model group, and the treatment groups according to random digit table, 50 in each group. Traumatic brain injury model was established by controlled cortical strike. Rats in the sham-operation group received surgery and anesthesia procedures only, with no strike. Muscone (1.8 mg/kg) was delivered to rats in the treatment group using in situ nasal perfusion, 30 min each time, twice daily for 7 successive days. Water content of brain tissue was detected in each group before intervention (T1), at day 3 of intervention (T2), day 5 of intervention (T3), and after intervention (T4), respectively. Expression levels of brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were detected using immunohistochemical analysis.

RESULTSCompared with the sham-operated group, water content of brain tissue increased (P < 0.05), and expression levels of NGF and BDNF decreased in the model group at T1, T2, T3, and T4 (P <0. 01). Compared with the model group, water content of brain tissue decreased (P < 0.05), and expression levels of NGF and BDNF increased (P < 0.01) in the treatment group at T1, T2, and T3.

CONCLUSIONNasal administration of muscone could reduce water content of brain tissue, alleviate cerebral edema, promote secretion of BDNF and NGF by olfactory ensheathing cells in traumatic brain injury rats.

Animals ; Brain ; drug effects ; Brain Injuries ; drug therapy ; Brain-Derived Neurotrophic Factor ; metabolism ; Cycloparaffins ; pharmacology ; Nerve Growth Factor ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the role of oxiracetam on traumatic brain injury in rats.

METHODSThirty Wistar rats were randomly divided into 3 groups: sham operation group, model group and treatment group. Feeney method were used to establish traumatic brain injury (TBI) model in rats in model and treatment group, and rats in sham group were only broached without hydraumatic fitted. Rats in treatment group were successive administration for 21 days with oxiracetam (100 mg/kg, ig). Neurologic impairment scores were undertook after operation of 1 d, 4 d, 7 d, 14 d and 21 d, and Morris water maze test were proceeded during 15 to 19 days after operation. Average escape latency, searching time in target quadrant and number of crossing target platform in rats were recorded.

RESULTSNeurologic impairment scores of rats in treatment group were significantly less than those of model group after operation of 7, 14 and 21 d (P < 0.05). Average escape latency of model group were significantly higher than those of sham operation group and treatment group (P < 0.05, P < 0.01). Searching time in target quadrant and number of crossing target platform of model group were lower than those of sham operation and treatment group (P < 0.05)).

CONCLUSIONOxiracetam could decrease neural injury and increase ability of learning, memory and space cognition in traumatic brain injury rats.

Animals ; Brain Injuries ; drug therapy ; psychology ; Male ; Maze Learning ; drug effects ; Pyrrolidines ; pharmacology ; therapeutic use ; Rats ; Rats, Wistar

OBJECTIVETo explore the effects of Xingnaojing injection on cerebral edema and blood-brain barrier (BBB) in rats following traumatic brain injury (TBI).

METHODSA total of 108 adult male Sprague-Dawley rats were used as subjects and randomly assigned to three groups: sham-operation, TBI and Xingnaojing injection groups (10 ml/kg/d, intraperitoneal injection). TBI in rats was set up by the improved device of Feeney's weight-dropping model with the impact of 600 g.cm. Brain water content and BBB permeability expressed as Evans blue content were measured at 1, 3, 5 and 7 days after surgery.

RESULTSIn sham-operation group, brain water content and Evans blue content in brain tissue were 78.97%+/-1.22% and 5.13 microgram+/-0.71 microgram. Following TBI, water content in brain tissue was increased significantly at 1, 3, 5 and 7 days (83.49%+/-0.54%, 82.74%+/-0.72%, 80.22%+/-0.68%, 79.21%+/-0.60%), being significantly higher than that in sham operation group (P less than 0.05). Evans blue content was increased in TBI group (16.54 microgram+/-0.60 microgram, 14.92 microgram+/-0.71 microgram, 12.44 microgram+/-0.92 microgram, 10.14 microgram+/-0.52 microgram) as compared with sham-operation group(P less than 0.05). After treatment with Xingnaojing injection, brain water content decreased as compared with TBI group (81.91%+/-1.04%, 80.38%+/-0.72%, 79.54%+/-0.58%, 78.60%+/-0.77%, P less than 0.05). Xingnaojing injection also reduced the leakage of BBB as compared with TBI group (15.11 microgram+/-0.63 microgram, 13.62 microgram+/-0.85 microgram, 10.06microgram+/-0.67 microgram, 9.54 microgram+/-0.41 microgram, P less than 0.05).

CONCLUSIONXingnaojing injection could alleviate cerebral edema following TBI via reducing permeability of BBB.

Animals ; Blood-Brain Barrier ; drug effects ; Brain ; pathology ; Brain Edema ; drug therapy ; Brain Injuries ; drug therapy ; pathology ; Drugs, Chinese Herbal ; administration & dosage ; Injections ; Male ; Medicine, Chinese Traditional ; Permeability ; Rats ; Rats, Sprague-Dawley

Neuroinflammation is a key contributor to the pathogenic cascades induced by hypoxic-ischemic (HI) insult in the neonatal brain. AD-16 is a novel anti-inflammatory compound, recently found to exert potent inhibition of the lipopolysaccharide-induced production of pro-inflammatory and neurotoxic mediators. In this study, we evaluated the effect of AD-16 on primary astrocytes and neurons under oxygen-glucose deprivation (OGD) in vitro and in mice with neonatal HI brain injury in vivo. We demonstrated that AD-16 protected against OGD-induced astrocytic and neuronal cell injury. Single dose post-treatment with AD-16 (1 mg/kg) improved the neurobehavioral outcome and reduced the infarct volume with a therapeutic window of up to 6 h. Chronic administration reduced the mortality rate and preserved whole-brain morphology following neonatal HI. The in vitro and in vivo effects suggest that AD-16 offers promising therapeutic efficacy in attenuating the progression of HI brain injury and protecting against the associated mortality and morbidity.
Animals ; Animals, Newborn ; Astrocytes/pathology* ; Brain/pathology* ; Brain Injuries/pathology* ; Glucose ; Hypoxia ; Hypoxia-Ischemia, Brain/drug therapy* ; Mice ; Neuroinflammatory Diseases ; Neuroprotective Agents/therapeutic use* ; Oxygen/therapeutic use*

Our study was designed to determine whether methylprednisolone exerts a beneficial effect after experimental moderate diffuse brain injury and whether this possible beneficial effect is affected by the dosage, the timing of administration, and the methods of treatment. A total of 200 anesthetized adult rats were injured utilizing a weight-drop device through a Plexiglas guide tube. These rats were divided into eight groups: Group 1 (n=35) was assigned to receive no methylprednisolone after impact (control group), Group 2 (n=25) received an initial intraperitoneal administration of methylprednisolone with a dose of 5 mg/kg at 1hour after cranial impact, followed by administration with a maintenance dose of 5 mg/kg/4 hours. Group 3 (n=25), group 5 (n=25), and group 7 (n=20) received an initial 30 mg/kg at 1 hour, 4 hours, and 8 hours, respectively without a maintenance dose. Group 4 (n=25), group 6 (n=25), and group 8 (n=20) received an initial 30 mg/kg at 1 hour, 4 hours, and 8 hours after impact, with a maintenance dose of 15 mg/kg/4 hours. Measured water content of brain tissue expressed the amount of water as the difference between fresh and dry weight. At 48 hours after impact, the water content in group 4 and 6 were significantly lower than group 1. Mean SD was 61.4 0.37% in group 4 (p<0.03), 61.5 0.34% in group 6 (p<0.001), and 63.6 0.48% in group 1. Compared to group 1, the difference was not statistically significant in group 2 (p>0.1), group 3 (p>0.5), group 5 (p>0.6), group 7 (p>0.1), and group 8 (p>0.5). Groups treated with mega dose before 4hours after head injury, including maintenance dose, showed beneficial effects. Our study suggests that the efficacy of methylprednisolone in head injury was related to the dosage, the timing of administration, and method of treatment.
Animal ; Brain Edema/prevention | control* ; Brain Injuries/drug therapy* ; Dose-Response Relationship, Drug ; Injections, Intraperitoneal ; Methylprednisolone/therapeutic use* ; Neuroprotective Agents/therapeutic use* ; Rats ; Rats, Sprague-Dawley

Multipotent neural stem cells (NSCs) are operationally defined by their ability to self-renew, to differentiate into cells of all glial and neuronal lineages throughout the neuraxis, and to populate developing or degenerating CNS regions. The recognition that NSCs that were propagated in culture could be reimplanted into the mammalian brain, where they might integrate appropriately throughout the mammalian CNS and stably express foreign genes, has unveiled a new role for neural transplantation and gene therapy and a possible strategy for addressing the CNS manifestations of diseases that heretofore had been refractory to intervention. Proliferating single cells were isolated from the telencephalic region of human fetal cadavers at 13 weeks of gestation and were grown as neurospheres in long-term cultures. We investigated the characteristics of the growth, differentiation, and region-specific gene expression of human NSCs. An intriguing phenomenon with possible therapeutic potentials has begun to emerge from our observations of the behavior of NSCs in animal models of neonatal hypoxic-ischemic brain and spinal cord injury. During phases of active neurodegeneration, factors seem to be transiently elaborated to which NSCs may respond by migrating to degenerating regions and differentiating specifically towards replacement of dying neural cells. NSCs may attempt to repopulate and reconstitute ablated regions. In addition, NSCs may serve as vehicles for gene delivery and appear capable of simultaneous neural cell replacement and gene therapy. After the approval of the Institutional Review Board of Severance Hospital, Yonsei University College of Medicine and Korean Food and Drug Administration, an investigator-sponsored clinical trial of the transplantation of human NSCs into patients with severe perinatal hypoxic ischemic brain injury and traumatic cervical motor complete spinal cord injury have been performed. The existing data from these clinical trials have shown to be safe, well tolerated, and of neurologically-some benefits.
Brain ; Brain Injuries ; Cadaver ; Ethics Committees, Research ; Gene Expression ; Genetic Therapy ; Humans ; Models, Animal ; Neural Stem Cells ; Neurodegenerative Diseases ; Neurons ; Pregnancy ; Spinal Cord ; Spinal Cord Injuries ; Tissue Therapy ; Transplants ; United States Food and Drug Administration

OBJECTIVETo explore the effect and mechanism of cinnabaris and realgar in promoting awake effect of endotoxin- induced brain injury rat applied with Angong Niuhuang Wan.

METHODNormal rats implanted cortical electrode in advance were divided into 6 groups: control, model, the Angong Niuhuang Wan (AGNH, 0.4, 0.2 g · kg(-1)), the Angong Niuhuang Wan without cinnabaris and realgar (QZX-AGNH, 0.32, 0.16 g · kg(-1)). Rats in the control and model groups were given distilled water. After three days of intragastric administration, the brain injury model was injected with endotoxin through tail vein. Then trace electro-corticogram (EcoG) 1-6 h after LPS injection, and compare the power and relative power of beta (β) and delta-waves (δ) at 6 h of these groups. The content of acetylcholine (Ach) and the affinity of M-receptor (M-R) in cortex and brainstem were detected by alkaline hydroxylamine colorimetric method and radioactive ligand binding assay, respectively.

RESULTAGNH (0.4, 0.2 g · kg(-1)) could increase the power and relative power of β and AGNH (0.4 g · kg(-1)) showed better action on brain electrical activation. QZX-AGNH showed weak effect on it. AGNH (0.4 g · kg(-1)) could increase the affinity of M-R in cortex and the content of Ach in brainstem. The action of QZX-AGNH was not obvious.

CONCLUSIONIn endotoxin-induced brain injury rats, AGNH can raise the cholinergic system function of cortex, and strengthen the uplink of cortex activation of brainstem cholinergic system, improve the level of cortical activity and enhance the activation of EcoG to promote the body's awakening. QZX-AGNH show weak effect. Cinnabaris and realgar play an important role in promoting awake effect in endotoxin-induced brain injury applied with Angong Niuhuang Wan. The mechanism may be related to cortical and brainstem cholinergic system function.

Animals ; Brain Injuries ; chemically induced ; drug therapy ; physiopathology ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; Endotoxins ; adverse effects ; Humans ; Male ; Rats ; Rats, Sprague-Dawley