Novel rodent models of penetrating traumatic brain injury

A penetrating traumatic brain injury（pTBI）occurs when an object impacts the head with sufficient energy to penetrate skin,cranial bone and meninges to inflict injury directly to the brain parenchyma.This type of injury is particularly common in areas plagued by armed conflicts or gun-related violence.

Animal model of repetitive mild traumatic brain injury for human traumatic axonal injury and chronic traumatic encephalopathy

Chronic traumatic encephalopathy（CTE）is a chronic neurodegenerative disease featured with tauopathy.CTE is tightly related with repetitive mild traumatic brain injury（m TBI）,which is interchangeably known as concussion（Mc Kee et al.,2009,2013）.This disease is differentiated by neuropathological features from other neurological diseases that involve tau protein aggregation and tangle formation abnormalities like Alzheimer＇s disease （AD）, frontotemporal dementia, and Parkinson- ism linked to chromosome 17 （FTDP-17）.

Better together? Treating traumatic brain injury with minocycline plus N-acetylcysteine

Traumatic brain injury has a complex pathophysiology that produces both rapid and delayed brain damage. Rapid damage initiates immediately after injury. Treatment of traumatic brain injury is typically delayed many hours, thus only delayed damage can be targeted with drugs. Delayed traumatic brain injury includes neuroinflammation, oxidative damage, apoptosis, and glutamate toxicity. Both the speed and complexity of traumatic brain injury pathophysiology present large obstacles to drug development. Repurposing of Food and Drug Administration-approved drugs may be a highly efficient approach to get therapeutics to the clinic. This review examines the preclinical outcomes of minocycline and N-acetylcysteine as individual drugs and compares them to the minocycline plus N-acetylcysteine combination. Both minocycline and N-acetylcysteine are Food and Drug Administration-approved drugs with pleiotropic therapeutic effects. As individual drugs, minocycline and N-acetylcysteine are well tolerated, with known pharmacokinetics, and enter the brain through an intact blood-brain barrier. At concentrations greater than needed for antimicrobial action, minocycline is a potent anti-inflammatory minocycline, also acts as an antioxidant and inhibits multiple enzymes that promote brain injury including metalloproteases, caspases, and polyADP-ribose-polymerase-1. N-acetylcysteine alone is also an antioxidant. It increases brain glutathione, prevents lipid oxidation, and protects mitochondria. N-acetylcysteine also acts as an anti-inflammatory as well as increases extracellular glutamate by activating the X;cystine-glutamate antitransporter. These multiple actions of minocycline and N-acetylcysteine have made them attractive candidates to treat traumatic brain injury. When first dosed within the one hour after injury, either minocycline or N-acetylcysteine improves a diverse set of therapeutic outcome measures in multiple traumatic brain injury animal models. A small number of clinical trials for traumatic brain injury have established the safety of minocycline or N-acetylcysteine and suggested that either drug has some efficacy. Preclinical studies have shown that minocycline plus N-acetylcysteine have positive synergy resulting in therapeutic effects and a more prolonged therapeutic time window not seen with the individual drugs. This review compares the actions of minocycline and N-acetylcysteine, individually and in combination. Evidence supports that the combination has greater utility to treat traumatic brain injury than the individual drugs.

A mouse model of weight-drop closed head injury:emphasis on cognitive and neurological deficiency

Traumatic brain injury（TBI） is a leading cause of death and disability in individuals worldwide.Producing a clinically relevant TBI model in small-sized animals remains fairly challenging.For good screening of potential therapeutics,which are effective in the treatment of TBI,animal models of TBI should be established and standardized.In this study,we established mouse models of closed head injury using the Shohami weight-drop method with some modifications concerning cognitive deficiency assessment and provided a detailed description of the severe TBI animal model.We found that 250 g falling weight from 2 cm height produced severe closed head injury in C57BL/6 male mice.Cognitive disorders in mice with severe closed head injury could be detected using passive avoidance test on day 7 after injury.Findings from this study indicate that weight-drop injury animal models are suitable for further screening of brain neuroprotectants and potentially are similar to those seen in human TBI.

Gliosis after traumatic brain injury in conditional ephrinB2-knockout mice

Background In response to the injury of the central nervous system （CNS）, the astrocytes upregulate the expression of glial fibrillary acidic protein （GFAP）, which largely contributes to the reactive gliosis after brain injury. The regulatory mechanism of this process is still not clear. In this study, we aimed to compare the ephrin-B2 deficient mice with the wild type ones with regard to qliosis after traumatic brain injury