Beneficial effect of agmatine on brain apoptosis, astrogliosis, and edema after rat transient cerebral ischemia.
BACKGROUND
Although agmatine therapy in a mouse model of transient focal cerebral ischemia is highly protective against neurological injury, the mechanisms underlying the protective effects of agmatine are not fully elucidated. This study aimed to investigate the effects of agmatine on brain apoptosis, astrogliosis and edema in the rats with transient cerebral ischemia.


METHODS
Following surgical induction of middle cerebral artery occlusion (MCAO) for 90 min, agmatine (100 mg/kg, i.p.) was injected 5 min after beginning of reperfusion and again once daily for the next 3 post-operative days. Four days after reperfusion, both motor and proprioception functions were assessed and then all rats were sacrificed for determination of brain infarct volume (2, 3, 5-triphenyltetrazolium chloride staining), apoptosis (TUNEL staining), edema (both cerebral water content and amounts of aquaporin-4 positive cells), gliosis (glial fibrillary acidic protein [GFAP]-positive cells), and neurotoxicity (inducible nitric oxide synthase [iNOS] expression).


RESULTS
The results showed that agmatine treatment was found to accelerate recovery of motor (from 55 degrees to 62 degrees) and proprioception (from 54% maximal possible effect to 10% maximal possible effect) deficits and to prevent brain infarction (from 370 mm3 to 50 mm3), gliosis (from 80 GFAP-positive cells to 30 GFAP-positive cells), edema (cerebral water contents decreased from 82.5% to 79.4%; AQP4 positive cells decreased from 140 to 84 per section), apoptosis (neuronal apoptotic cells decreased from 100 to 20 per section), and neurotoxicity (iNOS expression cells decreased from 64 to 7 per section) during MCAO ischemic injury in rats.


CONCLUSIONS
The data suggest that agmatine may improve outcomes of transient cerebral ischemia in rats by reducing brain apoptosis, astrogliosis and edema.
Wang
Che-Chuan
CC
Department of Surgery, Chi Mei Medical Center, Tainan 710, Taiwan.|Department of Biotechnology, Southern Taiwan University, Tainan 710, Taiwan.
Chio
Chung-Ching
CC
Department of Surgery, Chi Mei Medical Center, Tainan 710, Taiwan.
Chang
Ching-Hong
CH
Department of Surgery, Chi Mei Medical Center, Tainan 710, Taiwan.
Kuo
Jinn-Rung
JR
Department of Surgery, Chi Mei Medical Center, Tainan 710, Taiwan.|Department of Biotechnology, Southern Taiwan University, Tainan 710, Taiwan.
Chang
Ching-Ping
CP
Department of Biotechnology, Southern Taiwan University, Tainan 710, Taiwan.|Department of Medical Research, Chi Mei Medical Center, Tainan 710, Taiwan.
D000376:Agmatine / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051401:Aquaporin 4 / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001929:Brain Edema / Q000517:prevention & control*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000517:prevention & control*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009069:Movement Disorders / Q000188:drug therapy / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control; D012678:Sensation Disorders / Q000188:drug therapy / Q000517:prevention & control; D013997:Time Factors
C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D000376:Agmatine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat
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