Neuroprotective effects of dexmedetomidine on traumatic brain injury: Involvement of neuronal apoptosis and HSP70 expression.

The aim of the present study was to investigate the protective effect of dexmedetomidine (Dex) on traumatic brain injury (TBI), and further evaluate whether the underlying neuroprotective mechanisms are associated with neurological apoptosis and the expression of 70 kDa heat shock protein (HSP70) in the hippocampus. A total of 90 adult male Sprague­Dawley rats were randomly assigned into 3 groups (n=30/group): Sham, TBI and Dex groups. The rat models of TBI were established using a modified weight­drop device and Dex (15 µg/kg) was intravenously administered immediately following TBI. The brain edema and neurological function outcomes of TBI were assessed using wet­dry weight analysis and the Neurological Severity Score method. The expression levels of B­cell lymphoma­2 (Bcl­2) and Bcl­2­associated X protein (Bax) in the rat hippocampus were evaluated using immunohistochemical staining and western blot analysis. The protein levels of HSP70 in the hippocampal region were analyzed using western blot analysis. The results of the present study revealed that administration of Dex post­TBI improved brain edema and neurological outcomes, due to the attenuation of the TBI­induced reduction of Bax expression and increase of Bcl­2 and HSP70 expression. In conclusion, the results of the present study suggested that administration of Dex may serve as a neuroprotective agent against brain injury, at least partially via the inhibition of neuronal apoptosis and upregulation of HSP70 expression in the hippocampus.

Neuroprotective effects of resveratrol against traumatic brain injury in rats: Involvement of synaptic proteins and neuronal autophagy.

Traumatic brain injury (TBI) involves primary and secondary injury cascades that underlie delayed neuronal dysfunction and death, leading to long­term cognitive deficits, and effective therapeutic strategies targeting neuronal death remain elusive. The present study aimed to determine whether the administration of resveratrol (100 mg/kg) was able to significantly enhance functional recovery in a rat model of TBI and whether resveratrol treatment was able to upregulate synaptic protein expression and suppress post­TBI neuronal autophagy. The results demonstrated that daily treatment with resveratrol attenuated TBI­induced brain edema and improved spatial cognitive function and neurological impairment in rats. The expression of synaptic proteins was downregulated following TBI and this phenomenon was partly reversed by treatment with resveratrol. In addition, resveratrol was observed to significantly reduce the levels of the autophagic marker proteins, microtubule­associated protein light chain 3­II and Beclin1, in the hippocampus compared with the TBI group. Therefore, these results suggest that resveratrol may represent a novel therapeutic strategy for TBI, and that this protection may be associated with the upregulation of synaptophysin, postsynaptic density protein 95 and the suppression of neuronal autophagy.

Neuroprotective effects of brilliant blue G on the brain following traumatic brain injury in rats.

The P2X7 inhibitor, brilliant blue G (BBG), has been reported as a neuroprotective drug against a variety of disorders, including neuropathic pain and brain ischemia. Currently, no studies have examined the potential for BBG to provide neuroprotection in animal models of TBI. The aim of the present study was to investigate the neuroprotective effect of BBG on TBI and to determine the underlying mechanisms. The rats were subjected to a diffuse cortical impact injury caused by a modified weight-drop device, and then divided randomly into three groups: the sham-operated, BBG treatment and vehicle groups. In the BBG treatment group, 50 mg/kg brilliant blue G (BBG; 100% pure), a highly specific and clinically useful P2X7 antagonist, was administered via the tail vein 15 min prior to or up to 8 h following TBI. The co-localization of NeuN and protein kinase Cγ (PKCγ) was followed with immunofluorescent staining. The expression of P2X7, PKCγ and inflammatory cytokines was identified by western blot analysis. Wet-dry weight method was used to evaluate brain edema, and motor function outcome was examined using the neurological severity score. The present study demonstrated that the administration of BBG attenuated TBI-induced cerebral edema and the associated motor deficits. Following trauma, BBG treatment significantly reduced the levels of PKCγ and interleukin-1ß in the cortex. The results provide in vivo evidence that BBG exerted neuroprotective effects by attenuating brain edema and improving neurological functions via reducing PKCγ and interleukin-1ß levels following TBI.