Project description:Traumatic brain injury (TBI) induces a complex cascade of molecular and physiological effects. This study proposes to investigate the gene expression profile in cortex and hippocampus over early time points, following two different injury severities. These results will complement prior knowledge of both metabolic and neuroplastic changes after TBI, as well as serve as a starting point to investigate additional gene families whose expression is altered after TBI.,To characterize the profile of gene expression following a diffuse traumatic brain injury of varying severity in adult rats. ,Distinct patterns of gene expression following traumatic brain injury will occur in a time- and injury-dependent fashion. In particular, changes in expression of enzymes involved in energy metabolism and neuroplasticity will be detected.,Adult rats will be subjected to mild and severe lateral fluid percussion injury OR sham surgery without injury. At various post-injury timepoints (0.5, 4 and 24 hours), animals will be sacrificed, brain regions (parietal cortex and hippocampus, ipsilateral and contralateral to injury) will be dissected and RNA isolated. RNA will be used to synthesize cRNA probes for microarray hybridization. RNA from 2 matched animals will be pooled onto a single chip (U34A rat, Affymetrix). Comparisons will be made between sham and injured animals, with brain region, injury severity, and post-injury time point as the experimental variables.
Project description:Traumatic brain injury (TBI) alters and dysregulates the expression of thousands of genes in the brain. Since some of the most common problems in TBI patients are learning and memory deficits, we are studying the effects of TBI on the hippocampus, a region of the brain which is essential for learning and memory and which is known to be particularly vulnerable to TBI. We are interested in understanding how potential neuroprotective drugs alter the TBI-induced gene expression profile. The objective of this study is to elucidate and compare the differential gene expression profiles in the hippocampus of naive, sham-control, TBI and TBI plus drug treated rats. JM6, PMI-006 and E33 are three compounds with neuroprotective, anti-inflammatory and anti-oxidative effects. Our goal is to determine if different neuroprotective compounds have similar effects on common gene targets. These genes and the cell signaling pathways linked to them would then be the target of new therapeutic strategies for TBI. Rats were prepared for fluid percussion traumatic brain injury or sham injury (naïve rats had no anesthesia and were not handled in any way and gene expression in their brains serve as baseline data) and 24 hr post-injury, hippocampi were obtained, and stored in RNA later. Total RNA was isolated, quantitified and used for Agilent microarray analysis at GenUs Biosystems. Each group of naive, sham control, TBI and TBI plus JM6, TBI plus PMI-006 and TBI plus E33 (estrogen) has three biological replicates.
Project description:We investigated the therapeutic effect of the extracellular vesicles secreted by glial progenitor cells (GPC-EV) derived from human induced pluripotent stem cell in a traumatic brain injury model. The injury was modeled using the dosed concussion to the open brain method. The male Wistar rats were performed traumatic brain injury (TBI), and after 24 hours animals were randomly divided into two groups: group 1 — rats with intranasal administration of PBS (control), and group 2 — rats with similar administration of extracellular visicles (EV) derived from glial progenitor cells. miRNA PCR analysis of brain tissues ( cortex, striatum, hippocampus) were performed on postoperative day 7 to investigate miRNA associated with apoptosis, and inflammation.
Project description:We investigated the therapeutic effect of the extracellular vesicles secreted by glial progenitor cells (GPC-EV) derived from human induced pluripotent stem cell in a traumatic brain injury model. The injury was modeled using the dosed concussion to the open brain method. The male Wistar rats were performed traumatic brain injury (TBI), and after 24 hours animals were randomly divided into two groups: group 1 — rats with intranasal administration of PBS (control), and group 2 — rats with similar administration of extracellular visicles (EV) derived from glial progenitor cells. PCR analysis of brain tissues ( cortex, striatum, hippocampus) were performed on postoperative day 7 and 14 to investigate genes associated with apoptosis, and inflammation.
Project description:Traumatic brain injury (TBI) induces a complex cascade of molecular and physiological effects. This study proposes to investigate the gene expression profile in cortex and hippocampus over early time points, following two different injury severities. These results will complement prior knowledge of both metabolic and neuroplastic changes after TBI, as well as serve as a starting point to investigate additional gene families whose expression is altered after TBI. To characterize the profile of gene expression following a diffuse traumatic brain injury of varying severity in adult rats. Distinct patterns of gene expression following traumatic brain injury will occur in a time- and injury-dependent fashion. In particular, changes in expression of enzymes involved in energy metabolism and neuroplasticity will be detected. Adult rats will be subjected to mild and severe lateral fluid percussion injury OR sham surgery without injury. At various post-injury timepoints (0.5, 4 and 24 hours), animals will be sacrificed, brain regions (parietal cortex and hippocampus, ipsilateral and contralateral to injury) will be dissected and RNA isolated. RNA will be used to synthesize cRNA probes for microarray hybridization. RNA from 2 matched animals will be pooled onto a single chip (U34A rat, Affymetrix). Comparisons will be made between sham and injured animals, with brain region, injury severity, and post-injury time point as the experimental variables. Keywords: time-course