title: PACAP stimulates functional recovery after spinal cord injury through axonal regeneration.
abstract: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuroprotective peptide expressed in the central nervous system. Although many studies have shown a neuroprotective effect of PACAP, the mechanism of PACAP in the treatment of spinal cord injury (SCI) is yet to be elucidated. The purpose of this study was to examine the efficacy and underlying mechanism of PACAP in a mouse SCI model where PACAP was delivered via a biodegradable hydrogel. When PACAP or saline was delivered immediately after SCI, the functional motor recovery 14 days after SCI was significantly improved in the PACAP group compared with that in the saline group. Expression levels of messenger RNA (mRNA) for collapsin response mediator protein 2 (CRMP2), a factor related to axonal regeneration, were increased in the PACAP group 14 days after SCI compared with those in the saline group. A significantly increased number of CRMP2-positive cells were observed around the injury lesion in the PACAP group, while CRMP2 co-labeling with neuronal and oligodendrocyte markers was detected in intact spinal cord. Fourteen days after SCI, anterograde tracing revealed that a significantly increased number of neuronal fibers extended caudally from the lesion epicenter in the PACAP group. These results suggest that PACAP stimulates functional motor recovery after SCI through axonal regeneration mediated by CRMP2.
authors: Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
authors: Masashi
authors: M
authors: Tsuchida
authors: Tomoya
authors: T
authors: Nakamachi
authors: Kouichi
authors: K
authors: Sugiyama
authors: Daisuke
authors: D
authors: Tsuchikawa
authors: Jun
authors: J
authors: Watanabe
authors: Motohide
authors: M
authors: Hori
authors: Akira
authors: A
authors: Yoshikawa
authors: Nori
authors: N
authors: Imai
authors: Nobuyuki
authors: N
authors: Kagami
authors: Attila
authors: A
authors: Matkovits
authors: Takashi
authors: T
authors: Atsumi
authors: Seiji
authors: S
authors: Shioda
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology* / Q000627:therapeutic use; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000188:drug therapy*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C095114:collapsin response mediator protein-2