Expression of orexin-A (hypocretin-A) in the hypothalamus after traumatic brain injury: A postmortem evaluation

Traumatic brain injury (TBI) is one of the leading causes of mortality and morbidity. The key component of TBI pathophysiology is traumatic axonal injury (TAI), commonly referred to as diffuse axonal injury (DAI). Coma is a serious complication which can occur following traumatic brain injury (TBI). Recently, studies have shown that the central orexinergic/ hypocretinergic system exhibit prominent arousal promoting actions. Therefore, the purpose of this study is to investigate by immunohistochemistry the expression of beta-amyloid precursor protein (β-APP) in white matter of parasagittal region, corpus callosum and brainstem and the expression of orexin-A (ORXA) in the hypothalamus after traumatic brain injury. RESULTS: DAI was found in 26 (53.06%) cases, assessed with β-APP immunohistochemical staining in parasagittal white matter, corpus callosum and brainstem. Orexin-A immunoreactivity in hypothalamus was completely absent in 5 (10.2%) of the cases; moderate reduction of ORXA was observed in 9 (18.4%) of the cases; and severe reduction was observed in 7 (14.3%) of the cases. A statistically significant correlation was found between β-APP immunostaining in white matter, corpus callosum and brainstem in relation to survival time (p < 0.002, p < 0.003 and p < 0.005 respectively). A statistically positive correlation was noted between ORX-A immunoreactivity in hypothalamus to survival time (p < 0.003). An inverse correlation was noted between the expression of β-APP in the regions of brain studied to the expression of ORX-A in the hypothalamus of the cases studied (p < 0.005). CONCLUSIONS: The present study demonstrated by immunohistochemistry that reduction of orexin-A neurons in the hypothalamus, involved in coma status and arousal, enhanced the immunoexpression of β-APP in parasagital white matter, corpus callosum and brainstem.