Temporal Pattern of Neurodegeneration, Programmed Cell Death, and Neuroplastic Responses in the Thalamus After Lateral Fluid Percussion Brain Injury in the Rat

Abstract

The effects of traumatic brain injury (TBI) on the thalamus are not well characterized. We analyzed neuronal degeneration and loss, apoptosis, programmed cell death-executing pathways, and neuroplastic responses in the rat thalamus during the first week after lateral fluid percussion injury (LFPI). The most prominent neurodegenerative and neuroplastic changes were observed in the region containing the posterior thalamic nuclear group and ventral posteromedial and posterolateral thalamic nuclei ipsilateral to the LFPI. There was progressive neurodegeneration in these regions, with maximal neuronal loss on Day 7. Increases in numbers of apoptotic cells were detected on Day 1 and were enhanced on Days 3 and 7 after TBI. There was unchanged expression of active caspase-3 at all postinjury time points, but there was increased expression of apoptosis-inducing factor (AIF) on Day 7. The AIF nuclear translocation was detected on Day 1 and was maximal on Day 7. Total thalamic synaptophysin expression was unchanged, but immunostaining intensities were increased at all time points after TBI. Decreased growth-associated protein-43 expression and signal intensity were observed on Day 1. Our results suggest that progressive neuronal damage and loss, AIF signaling pathway-dependent programmed cell death, and limited neuroplastic changes occur in the rat thalamus during the first week after LFPI induction.

Chronic Upregulation of Cleaved-Caspase-3 Associated with Chronic Myelin Pathology and Microvascular Reorganization in the Thalamus after Traumatic Brain Injury in Rats

“…These studies documented upregulation of activated caspase-3 in the traumatized brain primarily in the cortex and hippocampus [50,51,52,53]. There is only limited preclinical evidence related to the subacute involvement of caspase-3-mediated apoptosis in the thalamus or other brain injury regions distal to the focal injury site [54,55,56]. To the best of our knowledge, there are no published data regarding chronic caspase-3-mediated pathways in these brain regions.…”

Analysis of Post-Traumatic Brain Injury Gene Expression Signature Reveals Tubulins, Nfe2l2, Nfkb, Cd44 and S100a4 as Treatment Targets

“…Genome-wide gene expression studies performed to date have largely focused on analysis of the perilesional cortex and ipsilateral hippocampus 8 9 10 , and only one study has reported findings from the thalamus 11 . Almost all studies have exclusively assessed the transcriptomics changes at the acute post-TBI phase, i.e., within 24–48 h post-injury 8 10 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 , and therefore provide limited information about the mechanisms that underlie functional recovery and epileptogenesis, which occur weeks to months post-TBI 30 .…”

Icariin Improves Functional Behavior in a Mouse Model of Traumatic Brain Injury and Promotes Synaptic Plasticity Markers

“…loss following TBI [20]. The current results suggest that icariin has little direct neuroprotective effect on TBI and that it might be inappropriate for the stage following TBI when neuronal death is predominant.…”