Cited by 45Mitochondrial Function and PathologyNeurological Disorders and TreatmentsTraumatic Brain Injury and Neurovascular Disturbances

Neuroprotective effect of Ro5-4864 following brain injury

Soustiel, Jean F., Zaaroor, Menashe, Vlodavsky, Eugene, Veenman, Leo, Weizman, Abraham, Gavish, Moshe·2008·Experimental Neurology

Abstract

The 18 kDa translocator protein (TSPO) is a protein complex located at the outer mitochondrial membrane and interacting with the mitochondrial permeability transition pore (mPTP), indicating its involvement in the control of mPTP opening. We intended to explore the effect of TSPO ligands, PK 11195 and Ro5-4864 on apoptosis in a rat model of cortical injury. Sprague-Dawley rats received a daily intraperitoneal injection of dimethylsulfoxide (vehicle), PK 11195, or Ro5-4864, starting 2 days prior the injury and a third injection after the injury. At 6 weeks, immunohistochemistry analysis showed that Ro5-4864 resulted in a significant increase in the number of surviving neurons and in the density of the neurofilament network in the perilesional cortex in comparison with animals of the vehicle and PK 11195 groups. In tissue samples dissected from the injured area, Ro5-4864 caused a significant reduction in activation of caspases 3 and 9 but not of caspase 8 in comparison with the vehicle and PK 11195 groups. In addition, measurements of transmembrane mitochondrial potential of mitochondria (Deltapsi(M)) isolated from normal rat brain showed that loss of Deltapsi(M) induced by recombinant Bax could be significantly reduced by Ro5-4864 in a concentration-dependent manner. Our findings indicate that the neuroprotective effect shown by Ro5-4864 in the present model of brain injury involves the mitochondrial pathway of apoptosis modulation of mPTP.

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Crossref · 10.1016/j.expneurol.2008.08.008

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Authors
Soustiel, J. F., Zaaroor, M., Vlodavsky, E., Veenman, L., Weizman, A., & Gavish, M.
Affiliations
  • Technion – Israel Institute of Technology (IL)
  • Tel Aviv University (IL)
Corresponding author
  • Soustiel, Jean F.
  • Gavish, Moshe
Venue
Experimental Neurology
Publisher
Elsevier BV
Published
2008-12
Volume
214
Issue
2
Pages
201-208
ISSN
0014-4886 (ISSN-L)
OpenAlex
W2064170262
Cited by
44
References
42
Citations by year
2026: 1 · 2025: 1 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 1 · 2012: 2
FWCI
1.50
Type
journal article
Language
en
Open access
closed
Locations
  • Experimental Neurology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
Ro5-4864, translocator protein (TSPO), PK11195, neuroprotection, brain injury, cortical injury, apoptosis, mitochondrial permeability transition pore, caspase-3, caspase-9, caspase-8, Bax, dimethyl sulfoxide
MeSH terms
Animals, Antineoplastic Agents, Benzodiazepinones, Brain Injuries, Carrier Proteins, Convulsants, Disease Models, Animal, Isoquinolines, Ligands, Male, Mitochondria, Neurons, Receptors, GABA-A, Rats, Sprague-Dawley, Apoptosis, Neuroprotective Agents, Caspases, Rats, Membrane Potential, Mitochondrial

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