Alpha-lipoic acid treatment is neurorestorative and promotes functional recovery after stroke in rats

Abstract

The antioxidant properties of alpha-lipoic acid (aLA) correlate with its ability to promote neuroproliferation. However, there have been no comprehensive studies examining the neurorestorative effects of aLA administration after the onset of ischemia. The middle cerebral artery (MCA) of adult rats was occluded for 2 hours and then reperfused. aLA (20 mg/kg) was administered in 71 animals (aLA group) through the left external jugular vein immediately after reperfusion. An equivalent volume of vehicle was administered to 71 animals (control group). Functional outcome, levels of endogenous neural precursors with neurogenesis, glial cell activation, and brain metabolism were evaluated. Immediate aLA administration after reperfusion resulted in significantly reduced mortality, infarct size, and neurological deficit score (NDS) in the test group compared to the control group. Long-term functional outcomes, measured by the rotarod test, were markedly improved by aLA treatment. There was a significant increase in the number of cells expressing nestin and GFAP in the boundary zone and infarct core regions after aLA treatment. Furthermore, significantly more BrdU/GFAP, BrdU/DCX, and BrdU/NeuN double-labeled cells were observed along the boundary zone of the aLA group on days 7, 14, and 28 days, respectively. And brain metabolism using 18F-FDG microPET imaging was markedly improved in aLA group. The effects of aLA was blocked by insulin receptor inhibitor, HNMPA (AM)3. These results indicate that immediate treatment with aLA after ischemic injury may have significant neurorestorative effects mediated at least partially via insulin receptor activation. Thus, aLA may be useful for the treatment of acute ischemic stroke.

α-Lipoic Acid Promotes Neurological Recovery After Ischemic Stroke by Activating the Nrf2/HO-1 Pathway to Attenuate Oxidative Damage

“…1D). Compared with the Control group, the LA20 group (10 [8, 12]) and LA40 group (13 [10, 15]) had significantly improved neurological outcomes (both P < 0.05). There was a statistical difference between the LA20 and LA40 groups, with the Garcia score in the LA40 group significantly improved ( P < 0.05).…”

“…These properties make LA a perfect antioxidant for the treatment of brain disease. The neuroprotective effect of LA has been demonstrated in different animal models of cerebral ischemia reperfusion injury [12, 30, 31]. Clark et al [30] demonstrated that LA pretreatment (100 mg/kg, subcutaneously) significantly reduced stroke infarct volume and promoted neurological function at 24 h post reperfusion in a focal cerebral reperfusion model.…”

“…In the study of Wu et al [36], the neuroportective of α-LA was attributed to inhibition of peripheral tumor necrosis factor-alpha and downregulation of brain microglial activation. In another research, the effect of α-LA was partially attributed to activation of insulin receptor because HNMPA-(AM)3, an insulin receptor inhibitor, blocked the neurorestorative effects of α-LA [12]. …”

“…Previous studies about the regulation of lipoic acid on ischemic stroke have been reported in animal models [11, 12] and in clinical study [13]. The cellular and molecular mechanisms associated with the protective effects of LA in ischemic stroke are partially be attributed to downregulation of microglial activation [11] and activation of insulin receptor [12]. In addition, LA attenuates cardiomyoctyes necrosis and apoptosis by activating the PI3K/Akt pathway as well as subsequent Nrf2 and HO-1 in experimental animal models of myocardial ischemia [14].…”

Immune System Involvement in the Degeneration, Neuroprotection, and Restoration after Stroke

“…For all these reasons, aL" is a great candidate to start clinical trials as neurorestorative of brain tissue [111].…”