Mesenchymal stem cells reduce long-term cognitive deficits and attenuate myelin disintegration and microglia activation following repetitive traumatic brain injury

The underlying mechanisms for the beneficial effects exerted by bone marrow-mesenchymal stem cells (BM-MSCs) in treating repetitive traumatic brain injury (rTBI)-induced long-term sensorimotor/cognitive impairments are not fully elucidated. Herein, we aimed to explore whether BM-MSCs therapy protect...

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Bibliographic Details
Published in:Science progress (1916) 2024-01, Vol.107 (1), p.368504241231154-368504241231154
Main Authors: Wang, Lan-Wan, Chio, Chung-Ching, Chao, Chien-Ming, Chao, Pi-Yu, Lin, Mao-Tsun, Chang, Ching-Ping, Lin, Hung-Jung
Format: Article
Language:English
Subjects:
Animals
Bone marrow
Brain
Brain Injuries, Traumatic - therapy
Cell therapy
Cognition
Cognitive ability
Cognitive Dysfunction
Damage accumulation
Disintegration
Head injuries
Histopathology
Immunofluorescence
Integrity
Mesenchymal Stem Cells
Microglia
Myelin
Myelin Sheath
Percussion
Rats
Sensorimotor system
Stem cells
Substantia alba
Substantia grisea
Therapy
Thickness
Trauma
Traumatic brain injury
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - pharmacology
Tumor necrosis factor-TNF
Tumor necrosis factor-α
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Summary:The underlying mechanisms for the beneficial effects exerted by bone marrow-mesenchymal stem cells (BM-MSCs) in treating repetitive traumatic brain injury (rTBI)-induced long-term sensorimotor/cognitive impairments are not fully elucidated. Herein, we aimed to explore whether BM-MSCs therapy protects against rTBI-induced long-term neurobehavioral disorders in rats via normalizing white matter integrity and gray matter microglial response. Rats were subjected to repeated mild lateral fluid percussion on day 0 and day 3. On the fourth day post-surgery, MSCs groups received MSCs (4 × 106 cells/ml/kg, intravenously) and were assessed by the radial maze, Y maze, passive avoidance tests, and modified neurological severity scores. Hematoxylin & eosin, and Luxol fast blue stainings were used to examine the histopathology and white matter thickness. At the same time, immunofluorescence staining was used to investigate the numbers of tumor necrosis factor-alpha (TNF-α)-containing microglia in gray matter. Three to nine months after neurotrauma, rats displayed sensorimotor and cognitive impairments, reduced thickness in white matter, and over-accumulation of TNF-α-containing microglia and cellular damage in gray matter. Therapy with BM-MSCs significantly attenuated the rTBI-induced sensorimotor and cognitive impairments and all their complications. Mesenchymal stem cell therapy might accelerate the recovery of sensorimotor and cognitive impairments in rats with rTBI via normalizing myelin integrity and microglia response.
ISSN:0036-8504
2047-7163
DOI:10.1177/00368504241231154