N-acetyl-L-leucine treatment attenuates neuronal cell death and suppresses neuroinflammation after traumatic brain injury in mice [article]

Chinmoy Sarkar, Nivedita Hegdekar, Marta M Lipinski
2019 bioRxiv   pre-print
Traumatic brain injury (TBI) is a major cause of mortality and long-term disability around the world. Even mild to moderate TBI can lead to lifelong neurological impairment due to acute and progressive neurodegeneration and neuroinflammation induced by the injury. Thus, the discovery of novel treatments which can be used as early therapeutic interventions following TBI is essential to restrict neuronal cell death and neuroinflammation. In this study, we demonstrate that orally administered
more » ... y administered treatment with N-acetyl-L-leucine (NALL) led to attenuation of cell death and reduced the expression of neuroinflammatory markers after controlled cortical impact (CCI) induced experimental TBI in mice. Our data indicate that partial restoration of autophagy flux mediated by NALL may account for the positive effect of treatment in the injured mouse brain. Taken together, our study indicates treatment with NALL would be expected to be beneficial in restricting neuronal death and hence improving neurological function after injury, and is a promising novel, neuroprotective drug candidate for the treatment of TBI.
doi:10.1101/759894 fatcat:6s7ja7pjcfc3fir25epls56dzm