Alph a lipoic acid protects against neural cell apoptosis in micefollowing traumatic brain injury / 医学研究生学报

ABSTRACT

Objective The prognosis of traumatic brain injury is closely associated with the apoptosis of neural cells .This study investigated the anti-apoptosis effect of alpha lipoic acid (α-LA) and its possible mechanism in the mouse model of traumatic brain injury. Methods Seventy-two healthy male ICR mice were randomly divided into four groups of 18 eachsham operation +vehicle, sham operation +α-LA, trauma +vehicle, and trauma +α-LA.The model of traumatic brain injury was made by weight-dropping.The animals in the α-LA groups were treated with intragastric α-LA at 30 minutes after surgery, while those in the vehicle groups with oral dimethyl sulfoxide in corn oil .At 48 hours after treatment , brain samples were collected from the mice for determining brain edema , measuring the expressions of cytochrome c , Bcl-2-associated X protein ( Bax ) , and caspase-3 in the mitochondria and cytosol of the brain tissue by Western blot and immunohistochemistry respectively , and detecting the survival of the neurons and apoptosis of neural cells in the cortical area by Nissl staining and TUNEL , re-spectively. Results The brain water volume , caspase-3 expres-sion, and neural cell apoptosis were markedly higher while the neuron survival remarkably lower in the trauma +vehicle group than in the sham operation +vehicle and sham operation +α-LA groups ( P<0.01).Compared with the mice in the trauma +vehicle group, those in the trauma +α-LA group showed significantly reduced proportion of water in the brain tissue ([79.89 ±0.55] vs [81.71 ± 0.66]%, P<0.05), expression of caspase-3 ([58.40 ±7.31] vs [47.42 ±7.74]%, P<0.05), and apoptosis of neural cells ([59.63 ±8.61] vs [44.86 ±7.32]%, P <0.05), but increased survival rate of neurons ([44.45 ±10.56] vs [57.46 ± 11.01]%, P<0.05).The expression of cytochrome c in the mitochondria was remarkably decreased and that of Bax markedly in -creased in the trauma +vehicle than in the sham operation +vehicle and sham operation +α-LA groups (P<0.01). Conclusion Alpha lipoic acid has a protective effect against traumatic brain injury in mice , probably by inhibiting the apoptosis of neural cells through the mitochondrial pathway .