Neuroprotective properties of aptiganel HCL (Cerestat) following controlled cortical impact injury.
Recent studies revealed a neuroprotective effect of the non-competitive NMDA receptor antagonist Aptiganel HCL (Cerestat CNS 1102) in focal cerebral ischemia. This study investigates the influence of Cerestat on contusion volume, post-traumatic brain edema and intracranial pressure (ICP) following Controlled Cortical Impact Injury (CCII). In rats (n = 54) CCII was applied to the left hemisphere using a pneumatic impactor. Cerestat (2 mg/kg i.v.) or vehicle was injected 15 min after injury animals were sacrificed 24 hours later. Contusion volume was measured planimetrically (n = 18). Hemispheric swelling and water content were determined gravimetrically (n = 20). ICP, mean arterial blood pressure (MABP) and cerebral perfusion pressure (CPP) were monitored for 30 min before sacrifice (n = 16). Cerestat reduced contusion volume from 77.3 +/- 5.8 mm3 to 66.8 +/- 3.9 mm3 (p < 0.05). Hemispheric swelling was also diminished from 11.1 +/- 0.8% to 8.2 +/- 1.4% as soon was water content (Cerestat 82.30 +/- 0.18% vs. control: 82.78 +/- 0.12%, p < 0.05). ICP was decreased by treatment from 31.7 +/- 3.5 mm Hg to 26.3 +/- 2.2 mm Hg and CPP was significantly improved (82.1 +/- 4.4 mm Hg vs 57.7 +/- 4.8 mm Hg; p < 0.05) 24 hours after injury. Cerestat administration was associated with decrease contusion volume, less hemispheric swelling, a lower ICP and increased CPP.
Kroppenstedt
S N
SN
Department of Neurosurgery, Virchow Medical Center, Humboldt University, Berlin, Federal Republic of Germany.
Schneider
G H
GH
Thomale
U W
UW
Unterberg
A W
AW
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001924:Brain Concussion / Q000473:pathology / Q000503:physiopathology*; D001929:Brain Edema / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D007427:Intracranial Pressure / Q000187:drug effects / Q000502:physiology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D006146:Guanidines; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; C079779:aptiganel