Abstract
Brain injury induces disruption of the blood-brain barrier, edema, and release of autodestructive factors that produce delayed neuronal damage. NAPSVIPQ (NAP), a femtomolar-acting peptide, is shown to be neuroprotective in a mouse model of closed head injury. NAP injection after injury reduced mortality and facilitated neurobehavioral recovery (P < 0.005). Edema was reduced by 70% in the NAP-treated mice (P < 0.01). Furthermore, in vivo magnetic resonance imaging demonstrated significant brain-tissue recovery in the NAP-treated animals. NAP treatment decreased tumor necrosis factor-α levels in the injured brain and was shown to protect pheochromocytoma (PC12 cells) against tumor necrosis factor-α-induced toxicity. Thus, NAP provides significant amelioration from the complex array of injuries elicited by head trauma.
Footnotes
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Send reprint requests to: Prof. E. Shohami, Department of Pharmacology, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, Israel. E-mail:esty{at}cc.huji.ac.il
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This study was supported in part by the US-Israel Binational Science Foundation and The Israel Science Foundation and the Institute for the Study of Aging. I.G. is the incumbent of the Lily and Avraham Gildor Chair for the Investigations of Growth Factors. E.S. is affiliated with the David R. Bloom Center for Pharmacy, The Hebrew University School of Pharmacy.
- Abbreviations:
- ADNP
- activity-dependent neuroprotective protein
- VIP
- vasoactive intestinal peptide
- ADNF-9
- Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SALLRSIPA)
- NAP
- Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln (NAPVSIPQ)
- CHI
- closed head injury
- TNFα
- tumor necrosis factor α
- NSS
- neurological severity score
- MRI
- magnetic resonance image
- NMDA
- N-methyl-d-aspartate
- APP
- amyloid precursor protein
- FOV
- field of view
- TR
- repetition time
- TE
- time to echo
- MTS
- (3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
- Received June 8, 2000.
- Accepted September 6, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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