Weight-Drop Method for Inducing Closed Head Diffuse Traumatic Brain Injury.

Traumatic brain injury (TBI) is one of the foremost causes of disability and death globally. Prerequisites for successful therapy of disabilities associated with TBI involved improved knowledge of the neurobiology of TBI, measurement of quantitative changes in recovery dynamics brought about by therapy, and the translation of quantitative methodologies and techniques that were successful in tracking recovery in preclinical models to human TBI. Frequently used animal models of TBI in research and development include controlled cortical impact, fluid percussion injury, blast injury, penetrating blast brain injury, and weight-drop impact acceleration models. Preclinical models of TBI benefit from controlled injury settings and the best prospects for biometric quantification of injury and therapy-induced gradual recovery from disabilities. Impact acceleration closed head TBI paradigm causes diffuse TBI (DTBI) without substantial focal brain lesions in rats. DTBI is linked to a significant rate of death, morbidity, and long-term disability. DTBI is difficult to diagnose at the time of hospitalization with imaging techniques making it challenging to take prompt therapeutic action. The weight-drop method without craniotomy is an impact acceleration closed head DTBI model that is used to induce mild/moderate diffuse brain injuries in rodents. Additionally, we have characterized neuropathological and neurobehavioral outcomes of the weight-drop model without craniotomy for inducing closed head DTBI of graded severity with a range of mass of weights (50-450 gm). This chapter also discusses techniques and protocols for measuring numerous functional disabilities and pathological changes in the brain brought on by DTBI.

Repositioning of an anti-depressant drug, agomelatine as therapy for brain injury induced by craniotomy.

Traumatic brain injury (TBI) leads to the disruption of blood-brain barrier integrity and therefore results in increased brain water content (brain edema). Brain edema is a significant factor for increased intracranial pressure (ICP), which ultimately causes functional disability and death. The decompressive craniotomy (DC) is a surgical procedure widely used for treating increased ICP following TBI. The life-saving craniotomy itself results in brain injury. The objective of this study is to investigate the effect of agomelatine against craniotomy induced brain injury. The craniotomy was performed by a variable speed micro-motor dental driller of 0.8 mm drill bit. The present study, in addition to blood-brain permeability, brain water content (edema) and histological examination of the brain, also estimated locomotor activity, oxidant, and antioxidant parameters. Results show that the craniotomy induced increase in the blood-brain barrier permeability, brain water content (edema), oxidative stress (lipid peroxide and nitric oxide) and impaired antioxidant mechanisms (superoxide dismutase, catalase, and reduced glutathione) in rats. The craniotomy was also found to increase neuronal cell death indicated by augmented chromatolysis and impaired locomotor activity. Administration of agomelatine after the craniotomy ameliorated histopathological, neurochemical and behavioral consequences of craniotomy. Thus agomelatine is effective against brain injury caused by craniotomy.