title: Agmatine-promoted angiogenesis, neurogenesis, and inhibition of gliosis-reduced traumatic brain injury in rats.
abstract: BACKGROUND
  The mechanisms of agmatine-induced neuroprotective effects in traumatic brain injury (TBI) remain unclear. This study was to test whether inhibition of gliosis, angiogenesis, and neurogenesis attenuating TBI could be agmatine stimulated.
  
  
  METHODS
  Anesthetized rats were randomly assigned to sham-operated group, TBI rats treated with saline (1 mL/kg, intraperitoneally), or TBI rats treated with agmatine (50 mg/kg, intraperitoneally). Saline or agmatine was injected 5 minutes after TBI and again once daily for the next 3 postoperative days.
  
  
  RESULTS
  Agmatine therapy in rats significantly attenuated TBI-induced motor function deficits (62° vs. 52° maximal angle) and cerebral infarction (88 mm vs. 216 mm), significantly reduced TBI-induced neuronal (9 NeuN-TUNEL double positive cells vs. 60 NeuN-TUNEL double positive cells) and glial (2 GFAP-TUNEL double positive cells vs. 20 GFAP-TUNEL double positive cells) apoptosis (increased TUNEL-positive and caspase-3-positive cells), neuronal loss (82 NeuN-positive cells vs. 60 NeuN-positive cells), gliosis (35 GFAP-positive cells vs. 72 GFAP-positive cells; 60 Iba1-positive cells vs. 90 Iba1-positive cells), and neurotoxicity (30 n-NOS-positive cells vs. 90 n-NOS-positive cells; 35 3-NT-positive cells vs. 90 3-NT-positive cells), and significantly promoted angiogenesis (3 BrdU/endothelial cells vs. 0.5 BrdU/endothelial cells; 50 vascular endothelial growth factor positive cells vs. 20 vascular endothelial growth factor-positive cells) and neurogenesis (27 BrdU/NeuN positive cells vs. 15 BrdU/NeuN positive cells).
  
  
  CONCLUSIONS
  Resultantly, agmatine therapy may attenuate TBI in rats via promoting angiogenesis, neurogenesis, and inhibition of gliosis.
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Cheng-Kung University, Tainan, Taiwan.
authors.forename: Jinn-Rung
authors.initials: JR
authors.lastname: Kuo
authors.forename: Chong-Jeh
authors.initials: CJ
authors.lastname: Lo
authors.forename: Ching-Ping
authors.initials: CP
authors.lastname: Chang
authors.forename: Kao-Chang
authors.initials: KC
authors.lastname: Lin
authors.forename: Mao-Tsun
authors.initials: MT
authors.lastname: Lin
authors.forename: Chung-Ching
authors.initials: CC
authors.lastname: Chio
mesh_terms: D000376:Agmatine / Q000627:therapeutic use*; D043925:Angiogenesis Inducing Agents / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D002544:Cerebral Infarction / Q000517:prevention & control; D005911:Gliosis / Q000517:prevention & control*; D020287:In Situ Nick-End Labeling; D008297:Male; D009069:Movement Disorders / Q000517:prevention & control; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D052248:Nitric Oxide Synthase Type I / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D043925:Angiogenesis Inducing Agents; D018696:Neuroprotective Agents; D000376:Agmatine; D052248:Nitric Oxide Synthase Type I