A peptide derived from activity-dependent neuroprotective protein (ADNP) ameliorates injury response in closed head injury in mice.
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-alpha levels in the injured brain and was shown to protect pheochromocytoma (PC12 cells) against tumor necrosis factor-alpha-induced toxicity. Thus, NAP provides significant amelioration from the complex array of injuries elicited by head trauma.
Beni-Adani
L
L
Department of Neurosurgery, The Hebrew University Hadassah Medical Center, Jerusalem, Israel.
Gozes
I
I
Cohen
Y
Y
Assaf
Y
Y
Steingart
R A
RA
Brenneman
D E
DE
Eizenberg
O
O
Trembolver
V
V
Shohami
E
E
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy / Q000473:pathology; D016489:Head Injuries, Closed / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D018398:Homeodomain Proteins; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use*; D016716:PC12 Cells; D010455:Peptides / Q000378:metabolism / Q000627:therapeutic use*; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity
C117632:Adnp protein, mouse; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha