Acetylcholine and choline dynamics provide early and late markers of traumatic brain injury

Abstract

We assessed acetylcholine (ACh) and choline (Ch) dynamics 2.5 h, 1, 4 and 14 days after cerebral cortex impact injury or craniotomy only in adult male Sprague-Dawley rats. Cortical endogenous ACh (D0ACh), endogenous free Ch (D0Ch), deuterium-labeled Ch (D4Ch), and ACh synthesized from D4Ch (D4ACh) were measured by gas-chromatography mass-spectrometry after intravenous injection of D4Ch followed in 1 min by microwave fixation of the brain. D0Ch increased in and around the impact up to 700% of control within 1 day after trauma. Smaller D0Ch increases were found in the cortex contralateral to the impact and in both hemispheres after craniotomy only. D4Ch contents increased to 200% in the impact and surrounding regions 4-14 days post-trauma, with lower increases 2.5 h post-trauma. D0ACh decreased at all times post-trauma in the impact center, and initially in the periphery and adjacent regions with a recovery at 14 days. Similar D0ACh decreases, although of lesser extent and magnitude were present in the craniotomy only group. D4ACh showed a peak at one day post-trauma in all regions studied in the impact and craniotomy groups. In conclusion, D0Ch tissue level was an early marker of trauma, while 14 days after trauma Ch uptake from blood was enhanced in and around the traumatized cortex. Craniotomy by itself induced a generalized increase in ACh turnover 1 day after this minimal trauma. Choline acetyltransferase activity was reduced in the impact center region but not affected in the adjacent and contralateral regions or by craniotomy.