Longitudinal Brain Structural, Neurochemical, and Behavioral Changes Following Traumatic Brain Injury in Immature Rat Brain with ALCAR Treatment.

Abstract

Pediatric survivors of traumatic brain injury (TBI) suffer from long-term neurologic disabilities, including deficits in memory and learning. Proton magnetic resonance spectroscopy (¹H-MRS) can assess alterations in brain neurochemical profile non-invasively in vivo over time. Our study aimed to evaluate (1) the longitudinal metabolic alterations in the hippocampus after TBI using in vivo ¹H-MRS and MRI in developing rat brain, and (2) test whether treatment with acetyl-L-carnitine (ALCAR) affects hippocampal metabolic profile. Using a controlled cortical impact model of TBI, we used post-natal day (PND) 21 rat pups and acquired longitudinal ¹H-MRS of the ipsilateral perilesional and contralateral hippocampi 2-4 h, 24 h, 72 h, 7 days, and 21 days post injury. Behavioral analysis was performed on post-injury days (Dpi) 3-7, 14, and 21-28. ALCAR treated rats received intraperitoneal administration (100 mg/kg) at 1 h, 4 h, 12 h, and 23 h post injury. Our results show that TBI in immature brain results in long-term structural and neurochemical alterations. TBI resulted in long-term decreased hippocampal volume and a reduction in levels of glutamate (Glu), glutamine (Gln),γ-aminobutyric acid (GABA), myo-inositol (Ins) and taurine (Tau) in the ipsilateral (injured) hippocampus up to 72 h post injury. In TBI + vehicle and TBI + ALCAR groups, N-acetyl-aspartate (NAA) remained decreased 21 days post injury. Treatment with ALCAR did not significantly change hippocampal neurochemical profile at 24 h post injury. Behavioral studies in TBI-injured rats demonstrated that sensory motor function decreased initially and recovered with time. The TBI + ALCAR group performed significantly better compared to TBI + vehicle group in both sensory motor and hippocampal dependent recognition memory. Further studies with the longer duration of ALCAR administration are necessary to adequately assess the efficacy of ALCAR following pediatric TBI.