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Rho kinase inhibition following traumatic brain injury in mice promotes functional improvement and acute neuron survival but has little effect on neurogenesis, glial responses or neuroinflammation.
Exp Neurol. 2016 May; 279:86-95.EN

Abstract

Inhibition of the Rho/Rho kinase pathway has been shown to be beneficial in a variety of neural injuries and diseases. In this manuscript we investigate the role of Rho kinase inhibition in recovery from traumatic brain injury using a controlled cortical impact model in mice. Mice subjected to a moderately severe TBI were treated for 1 or 4 weeks with the Rho kinase inhibitor Y27632, and functional outcomes and neuronal and glial cell responses were analysed at 1, 7 and 35 days post-injury. We hypothesised that Y27632-treated mice would show functional improvement, with augmented recruitment of neuroblasts from the SVZ and enhanced survival of newborn neurons in the pericontusional cortex, with protection against neuronal degeneration, neuroinflammation and modulation of astrocyte reactivity and blood-brain-barrier permeability. While Rho kinase inhibition enhanced recovery of motor function after trauma, there were no substantial increases in the recruitment of DCX(+) neuroblasts or the number of BrdU(+) or EdU(+) labelled newborn neurons in the pericontusional cortex of Y27632-treated mice. Inhibition of Rho kinase significantly reduced the number of degenerating cortical neurons at 1day post-injury compared to saline controls but had no longer term effect on neuronal degeneration, with only modest effects on astrocytic reactivity and macrophage/microglial responses. Overall, this study showed that Rho kinase contributes to acute neurodegenerative processes in the injured cortex but does not play a significant role in SVZ neural precursor cell-derived adult neurogenesis, glial responses or blood-brain barrier permeability following a moderately severe brain injury.

Authors+Show Affiliations

Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC, Australia.Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC, Australia.Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC, Australia.Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC, Australia.Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC, Australia. Electronic address: turnley@unimelb.edu.au.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26896832

Citation

Bye, Nicole, et al. "Rho Kinase Inhibition Following Traumatic Brain Injury in Mice Promotes Functional Improvement and Acute Neuron Survival but Has Little Effect On Neurogenesis, Glial Responses or Neuroinflammation." Experimental Neurology, vol. 279, 2016, pp. 86-95.
Bye N, Christie KJ, Turbic A, et al. Rho kinase inhibition following traumatic brain injury in mice promotes functional improvement and acute neuron survival but has little effect on neurogenesis, glial responses or neuroinflammation. Exp Neurol. 2016;279:86-95.
Bye, N., Christie, K. J., Turbic, A., Basrai, H. S., & Turnley, A. M. (2016). Rho kinase inhibition following traumatic brain injury in mice promotes functional improvement and acute neuron survival but has little effect on neurogenesis, glial responses or neuroinflammation. Experimental Neurology, 279, 86-95. https://doi.org/10.1016/j.expneurol.2016.02.012
Bye N, et al. Rho Kinase Inhibition Following Traumatic Brain Injury in Mice Promotes Functional Improvement and Acute Neuron Survival but Has Little Effect On Neurogenesis, Glial Responses or Neuroinflammation. Exp Neurol. 2016;279:86-95. PubMed PMID: 26896832.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rho kinase inhibition following traumatic brain injury in mice promotes functional improvement and acute neuron survival but has little effect on neurogenesis, glial responses or neuroinflammation. AU - Bye,Nicole, AU - Christie,Kimberly J, AU - Turbic,Alisa, AU - Basrai,Harleen S, AU - Turnley,Ann M, Y1 - 2016/02/16/ PY - 2015/12/10/received PY - 2016/02/08/revised PY - 2016/02/15/accepted PY - 2016/2/21/entrez PY - 2016/2/21/pubmed PY - 2016/9/7/medline KW - Astrocytic gliosis KW - Controlled cortical impact KW - Fasudil KW - Horizontal ladder test KW - Microglia KW - NeuN KW - Rho GTPase KW - Y27632 SP - 86 EP - 95 JF - Experimental neurology JO - Exp. Neurol. VL - 279 N2 - Inhibition of the Rho/Rho kinase pathway has been shown to be beneficial in a variety of neural injuries and diseases. In this manuscript we investigate the role of Rho kinase inhibition in recovery from traumatic brain injury using a controlled cortical impact model in mice. Mice subjected to a moderately severe TBI were treated for 1 or 4 weeks with the Rho kinase inhibitor Y27632, and functional outcomes and neuronal and glial cell responses were analysed at 1, 7 and 35 days post-injury. We hypothesised that Y27632-treated mice would show functional improvement, with augmented recruitment of neuroblasts from the SVZ and enhanced survival of newborn neurons in the pericontusional cortex, with protection against neuronal degeneration, neuroinflammation and modulation of astrocyte reactivity and blood-brain-barrier permeability. While Rho kinase inhibition enhanced recovery of motor function after trauma, there were no substantial increases in the recruitment of DCX(+) neuroblasts or the number of BrdU(+) or EdU(+) labelled newborn neurons in the pericontusional cortex of Y27632-treated mice. Inhibition of Rho kinase significantly reduced the number of degenerating cortical neurons at 1day post-injury compared to saline controls but had no longer term effect on neuronal degeneration, with only modest effects on astrocytic reactivity and macrophage/microglial responses. Overall, this study showed that Rho kinase contributes to acute neurodegenerative processes in the injured cortex but does not play a significant role in SVZ neural precursor cell-derived adult neurogenesis, glial responses or blood-brain barrier permeability following a moderately severe brain injury. SN - 1090-2430 UR - https://www.unboundmedicine.com/medline/citation/26896832/Rho_kinase_inhibition_following_traumatic_brain_injury_in_mice_promotes_functional_improvement_and_acute_neuron_survival_but_has_little_effect_on_neurogenesis_glial_responses_or_neuroinflammation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(16)30034-6 DB - PRIME DP - Unbound Medicine ER -