The effect of blood glutamate scavengers oxaloacetate and pyruvate on neurological outcome in a rat model of subarachnoid hemorrhage.
Blood glutamate scavengers have been shown to effectively reduce blood glutamate concentrations and improve neurological outcome after traumatic brain injury and stroke in rats. This study investigates the efficacy of blood glutamate scavengers oxaloacetate and pyruvate in the treatment of subarachnoid hemorrhage (SAH) in rats. Isotonic saline, 250 mg/kg oxaloacetate, or 125 mg/kg pyruvate was injected intravenously in 60 rats, 60 minutes after induction of SAH at a rate of 0.1 ml/100 g/min for 30 minutes. There were 20 additional rats that were used as a sham-operated group. Blood samples were collected at baseline and 90 minutes after SAH. Neurological performance was assessed at 24 h after SAH. In half of the rats, glutamate concentrations in the cerebrospinal fluid were measured 24 h after SAH. For the remaining half, the blood brain barrier permeability in the frontal and parieto-occipital lobes was measured 48 h after SAH. Blood glutamate levels were reduced in rats treated with oxaloacetate or pyruvate at 90 minutes after SAH (p < 0.001). Cerebrospinal fluid glutamate was reduced in rats treated with pyruvate (p < 0.05). Neurological performance was significantly improved in rats treated with oxaloacetate (p < 0.05) or pyruvate (p < 0.01). The breakdown of the blood brain barrier was reduced in the frontal lobe in rats treated with pyruvate (p < 0.05) and in the parieto-occipital lobes in rats treated with either pyruvate (p < 0.01) or oxaloacetate (p < 0.01). This study demonstrates the effectiveness of blood glutamate scavengers oxaloacetate and pyruvate as a therapeutic neuroprotective strategy in a rat model of SAH.
Department of Anesthesiology and Critical Care, Soroka Medical Center, Ben Gurion University of the Negev, Faculty of Health Sciences, Beer Sheva 84005, Israel.
Matthew
M
Boyko
Israel
I
Melamed
Benjamin Fredrick
BF
Gruenbaum
Shaun Evan
SE
Gruenbaum
Sharon
S
Ohayon
Akiva
A
Leibowitz
Evgeny
E
Brotfain
Yoram
Y
Shapira
Alexander
A
Zlotnik
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000097:blood / Q000134:cerebrospinal fluid; D008297:Male; D009422:Nervous System Diseases / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000209:etiology*; D062907:Oxaloacetic Acid / Q000097:blood / Q000627:therapeutic use*; D019289:Pyruvic Acid / Q000097:blood / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000134:cerebrospinal fluid / Q000150:complications* / Q000188:drug therapy; D013997:Time Factors
D000975:Antioxidants; D062907:Oxaloacetic Acid; D018698:Glutamic Acid; D019289:Pyruvic Acid