To determine the exact role of TGF-alpha in glial activation after traumatic brain injury, we investigated the astroglial and microglial responses after cortical stab wound injury in TGF-alpha overexpressing mice. Adult male B6D2-TgN (MMTVTGFA) 29RjC transgenic mice were used for the subjects. This transgenic line carries a TGF-alpha cDNA under the control of the dexamethasone-inducible MMTV promoter. Thus, exogenous administration of dexamethasone induces TGF-alpha overexpression. Male B6D2F1/J mice at the same age served as wild-type animals. After the cortical stab wound injury, expression of glial fibrillary acidic protein, CD-11b and interleukine-6 were investigated immunohistochemically. The results indicate that TGF-alpha might affect astrocytic hypertrophy without affecting microgliosis not only in the normal condition, but also in the pathological condition. Moreover, overexpression of TGF-alpha induced obvious expression of IL-6 around the lesion. This fact might indicate possible role of TGF-alpha in affecting neuronal function.
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http://dx.doi.org/10.1179/016164103101201814 | DOI Listing |
Neural Regen Res
June 2025
GHM Institute of CNS Regeneration, Jinan University, Guangzhou, Guangdong Province, China.
JOURNAL/nrgr/04.03/01300535-202506000-00030/figure1/v/2024-08-05T133530Z/r/image-tiff Direct in vivo conversion of astrocytes into functional new neurons induced by neural transcription factors has been recognized as a potential new therapeutic intervention for neural injury and degenerative disorders. However, a few recent studies have claimed that neural transcription factors cannot convert astrocytes into neurons, attributing the converted neurons to pre-existing neurons mis-expressing transgenes.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
May 2024
Department of Developmental Biology and Cancer Research, The Institute for Medical Research-Israel-Canada, Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel.
After central nervous system injury, a rapid cellular and molecular response is induced. This response can be both beneficial and detrimental to neuronal survival in the first few days and increases the risk for neurodegeneration if persistent. Semaphorin4B (Sema4B), a transmembrane protein primarily expressed by cortical astrocytes, has been shown to play a role in neuronal cell death following injury.
View Article and Find Full Text PDFNat Commun
April 2024
Chair of Cell Biology and Anatomy, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Planegg-Martinsried, Germany.
Traumatic brain injury leads to a highly orchestrated immune- and glial cell response partially responsible for long-lasting disability and the development of secondary neurodegenerative diseases. A holistic understanding of the mechanisms controlling the responses of specific cell types and their crosstalk is required to develop an efficient strategy for better regeneration. Here, we combine spatial and single-cell transcriptomics to chart the transcriptomic signature of the injured male murine cerebral cortex, and identify specific states of different glial cells contributing to this signature.
View Article and Find Full Text PDFInt J Mol Sci
January 2024
Department of Pharmaceutical Sciences, University of Oklahoma College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA.
Traumatic brain injury (TBI) is a major cause of mortality and disability around the world, for which no treatment has been found. Nociceptin/Orphanin FQ (N/OFQ) and the nociceptin opioid peptide (NOP) receptor are rapidly increased in response to fluid percussion, stab injury, and controlled cortical impact (CCI) TBI. TBI-induced upregulation of N/OFQ contributes to cerebrovascular impairment, increased excitotoxicity, and neurobehavioral deficits.
View Article and Find Full Text PDFFront Mol Neurosci
April 2023
Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
In response to traumatic brain injury, a subpopulation of cortical astrocytes is activated, resulting in acquisition of stem cell properties, known as reactive astrocytes-derived progenitor cells (Rad-PCs). However, the underlying mechanisms remain largely unknown during this process. In this study, we examined the role of N-myc downstream-regulated gene 2 (NDRG2), a differentiation- and stress-associated molecule, in Rad-PCs after cortical stab injury in adult rats.
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