Faculty, Staff and Student Publications
Publication Date
9-1-2023
Journal
Experimental Neurology
Abstract
Background: Inflammation and white matter injury are consequences of neonatal intraventricular hemorrhage (IVH). Both white matter and the neuroimmune system are developing during the time which IVH occurs and its consequences develop. IVH has been studied in many different animal models; however, the effects of IVH occurring at different developmental time points in the same model have not been examined. Understanding how the timing of IVH affects outcome may provide important insights into both IVH pathophysiology and innate immune development.
Methods: We used intraventricular injection of lysed whole blood to model neonatal IVH in postnatal day (P)2 and P5 rats. Flow cytometry was used to detect innate immune activation. MRI was used to screen animals for the development of increased ventricular size. Immunohistochemistry for myelin basic protein was used to quantify white matter and corpus callosum thickness.
Results: P5 animals exhibited significant increases in several measures of classically pro-inflammatory innate immune activation that P2 animals did not. Animals with IVH induced at P5 also developed ventricular enlargement visible on MRI whereas animals with IVH induced at P2 did not. On histological analysis, there were no significant effects of IVH in P2 animals, but IVH in P5 animals reduced white matter labeling and corpus callosum thickness.
Conclusions: IVH induces a strong innate inflammatory response in P5 as well as changes in ventricular size and reduction of white matter. P2 animals do not exhibit significant changes in innate immune activation or white matter structure after IVH. This suggests that white matter pathology from IVH is due in part to innate immune activation; and that the developmental stage of the innate immune system is a key determinant of IVH pathology.
Keywords
Animals, Rats, White Matter, Cerebral Hemorrhage, Magnetic Resonance Imaging, Corpus Callosum, Immunity, Innate, Intraventricular hemorrhage, Hydrocephalus, Innate immunity, White matter, Oligodendrocyte
DOI
10.1016/j.expneurol.2023.114472
PMID
37336344
PMCID
PMC11718405
PubMedCentral® Posted Date
1-10-2025
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes