Understanding mechanisms of injury and repair in the developing brain remains a challenge. Damage is the result of an acute injury and of subsequent modifications in brain development.
The aim of the present study was to define the nature of acute and subsequent brain neurochemical profile alterations in a model of neonatal hypoxic-ischemic injury (HI) in the P3 rat pup using high-field MR imaging and spectroscopic techniques.
P3 Wistar pups underwent moderate (HI) injury consisting of right carotid cauterization, and hypoxia for 30 minutes at 6% O2. 24 hours (P4, n = 8) and 8 days after HI (P11, n = 8) MRI and 1H-MRS was performed using a 9.4T magnet. 1H-MRS spectra within the ipsilateral and contralateral cortex were acquired.
Injury was seen as an hyperintense signal in the ispilateral cortex. The volume of the brain in the HI group compared to the control was not significantly different at P4 but was reduced at P11. At P4 the neurochemical profile of the ipsilateral cortex indicated significant decreases of several metabolites (macromolecules, phosphocholine, creatine, inositol, N-acetyl aspartate, taurine, glutamate, glutamate/glutamine) reflecting an acute energetic and functional slowing-down in the injured cortex. At P11, only a few metabolites showed significant increase (phosphocreatine, glutamate, taurine, glutamate/glutamine). At P11, the variation of the metabolite concentrations need to be further investigated to define their role in this context.
These results provide new in vivo insight into the neurochemical processes resulting from HI in the developing brain that can be used to monitor injury and the response to protective therapies.