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Prophylactic treatment with CN-105 improves functional outcomes in a murine model of closed head injury.

Publication ,  Journal Article
Van Wyck, D; Kolls, BJ; Wang, H; Cantillana, V; Maughan, M; Laskowitz, DT
Published in: Exp Brain Res
September 2022

The treatment of traumatic brain injury (TBI) in military populations is hindered by underreporting and underdiagnosis. Clinical symptoms and outcomes may be mitigated with an effective pre-injury prophylaxis. This study evaluates whether CN-105, a 5-amino acid apolipoprotein E (ApoE) mimetic peptide previously shown to modify the post-traumatic neuroinflammatory response, would maintain its neuroprotective effects if administered prior to closed-head injury in a clinically relevant murine model. CN-105 was synthesized by Polypeptide Inc. (San Diego, CA) and administered to C57-BL/6 mice intravenously (IV) and/or by intraperitoneal (IP) injection at various time points prior to injury while vehicle treated animals received IV and/or IP normal saline. Animals were randomized following injury and behavioral observations were conducted by investigators blinded to treatment. Vestibulomotor function was assessed using an automated Rotarod (Ugo Basile, Comerio, Italy), and hippocampal microglial activation was assessed using F4/80 immunohistochemical staining in treated and untreated mice 7 days post-TBI. Separate, in vivo assessments of the pharmacokinetics was performed in healthy CD-1. IV CN-105 administered prior to head injury improved vestibulomotor function compared to vehicle control-treated animals. CN-105 co-administered by IP and IV dosing 6 h prior to injury also improved vestibulomotor function up to 28 days following injury. Microglia counted in CN-105 treated specimens were significantly fewer (P = 0.03) than in vehicle specimens. CN-105 improves functional outcomes and reduces hippocampal microglial activation when administered prior to injury and could be adapted as a pre-injury prophylaxis for soldiers at high risk for TBI.

Duke Scholars

Published In

Exp Brain Res

DOI

EISSN

1432-1106

Publication Date

September 2022

Volume

240

Issue

9

Start / End Page

2413 / 2423

Location

Germany

Related Subject Headings

  • Neuroprotective Agents
  • Neurology & Neurosurgery
  • Microglia
  • Mice, Inbred C57BL
  • Mice
  • Head Injuries, Closed
  • Disease Models, Animal
  • Brain Injuries, Traumatic
  • Animals
  • 3209 Neurosciences
 

Citation

APA
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Van Wyck, D., Kolls, B. J., Wang, H., Cantillana, V., Maughan, M., & Laskowitz, D. T. (2022). Prophylactic treatment with CN-105 improves functional outcomes in a murine model of closed head injury. Exp Brain Res, 240(9), 2413–2423. https://doi.org/10.1007/s00221-022-06417-4
Van Wyck, David, Bradley J. Kolls, Haichen Wang, Viviana Cantillana, Maureen Maughan, and Daniel T. Laskowitz. “Prophylactic treatment with CN-105 improves functional outcomes in a murine model of closed head injury.Exp Brain Res 240, no. 9 (September 2022): 2413–23. https://doi.org/10.1007/s00221-022-06417-4.
Van Wyck D, Kolls BJ, Wang H, Cantillana V, Maughan M, Laskowitz DT. Prophylactic treatment with CN-105 improves functional outcomes in a murine model of closed head injury. Exp Brain Res. 2022 Sep;240(9):2413–23.
Van Wyck, David, et al. “Prophylactic treatment with CN-105 improves functional outcomes in a murine model of closed head injury.Exp Brain Res, vol. 240, no. 9, Sept. 2022, pp. 2413–23. Pubmed, doi:10.1007/s00221-022-06417-4.
Van Wyck D, Kolls BJ, Wang H, Cantillana V, Maughan M, Laskowitz DT. Prophylactic treatment with CN-105 improves functional outcomes in a murine model of closed head injury. Exp Brain Res. 2022 Sep;240(9):2413–2423.
Journal cover image

Published In

Exp Brain Res

DOI

EISSN

1432-1106

Publication Date

September 2022

Volume

240

Issue

9

Start / End Page

2413 / 2423

Location

Germany

Related Subject Headings

  • Neuroprotective Agents
  • Neurology & Neurosurgery
  • Microglia
  • Mice, Inbred C57BL
  • Mice
  • Head Injuries, Closed
  • Disease Models, Animal
  • Brain Injuries, Traumatic
  • Animals
  • 3209 Neurosciences