The protective effect of alpha lipoic acid against traumatic brain injury in rats.
Traumatic brain injury (TBI) was induced by a weight-drop device using 300 g-1 m weight-height impact. The study groups were: control, alpha-lipoic acid (LA) (100 mg/kg, po), TBI, and TBI + LA (100 mg/kg, po). Forty-eight hours after the injury, neurological scores were measured and brain samples were taken for histological examination or determination of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) levels, myeloperoxidase (MPO) and Na(+)-K(+) ATPase activities, whereas cytokines (TNF-alpha, IL-1beta) were determined in blood. Brain oedema was evaluated by wet-dry weight method and blood-brain barrier (BBB) permeability was evaluated by Evans Blue (EB) extravasation. As a result, neurological scores mildly increased in trauma groups. Moreover, TBI caused a significant decrease in brain GSH and Na(+)-K(+) ATPase activity, which was accompanied with significant increases in TBARS level, MPO activity and plasma proinflammatory cytokines. LA treatment reversed all these biochemical indices as well as histopathological alterations. TBI also caused a significant increase in brain water content and EB extravasation which were partially reversed by LA treatment. These findings suggest that LA exerts neuroprotection by preserving BBB permeability and by reducing brain oedema probably by its anti-inflammatory and antioxidant properties in the TBI model.
Toklu
Hale Z
HZ
Marmara University, School of Pharmacy, Department of Pharmacology, Istanbul, Turkey.
Hakan
Tayfun
T
Biber
Necat
N
Solakoğlu
Seyhun
S
Oğünç
Ayliz Velioğlu
AV
Sener
Göksel
G
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001812:Blood-Brain Barrier; D001929:Brain Edema / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005978:Glutathione / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D008063:Thioctic Acid; D009195:Peroxidase; D005978:Glutathione