Neuroprotective effects of clarithromycin against neuronal damage in cerebral ischemia and in cultured neuronal cells after oxygen-glucose deprivation.
OBJECTIVE
Rats subjected to transient focal ischemia and cultured neuronal cells subjected to oxygen-glucose deprivation (OGD) were treated with clarithromycin (CAM) to evaluate the effects of CAM in protecting against neuronal damage.


METHODS
Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 90min and then reperfused. Each animal was given an oral dose clarithromycin (CAM, 100mg/kg) or vehicle alone just after the ischemia was commenced. The infarct volume, edema index and neurological performance were assessed after 24 and 72h of reperfusion. The cerebral blood flow (CBF) was measured with an MRI system at 90min after MCAO. After 24 and 72h, oxidative stress (4-HNE, 8-OHdG) and inflammation (Iba-1, TNF-α) were assessed by immunohistochemical analyses and degenerative cells were assessed in the cortex by Fluoro-Jade C (FJC) labeling. The cultured neuronal cells were also used to examine the effects of CAM exposure on the viability of the cells after OGD.


RESULTS
CBF was unchanged between the two groups. Significant reductions of the infarct volume and edema index, an improved neurological deficit score, a significant suppression of 4-HNE and 8-OHdG expression, marked reductions of Iba-1 and TNF-α expression, and a significant reduction of FJC-positive cells were also observed in the CAM-treated animals at both time points. Treatment with 10μM and 100μM CAM in vitro significantly reduced cell death after OGD.


CONCLUSIONS
CAM appears to provide antioxidant and anti-inflammatory effects and protect against neuronal damage after cerebral ischemia and OGD.
Department of Neurology and Stroke Center, Tokyo General Hospital, 3-15-2 Ekoda Nakano-ku, Tokyo 165-8906, Japan; Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo 113-8603, Japan. Electronic address: yasuo.katayama@mt.strins.or.jp.
Yasuo
Y
Katayama
Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo 113-8603, Japan.
Toshiki
T
Inaba
Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo 113-8603, Japan.
Chikako
C
Nito
Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo 113-8603, Japan.
Satoshi
S
Suda
Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo 113-8603, Japan.
Masayuki
M
Ueda
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation / Q000187:drug effects; D017291:Clarithromycin / Q000494:pharmacology / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018696:Neuroprotective Agents; D017291:Clarithromycin; D005947:Glucose; D010100:Oxygen
Anti-inflammatory action; Antioxidant action; Clarithromycin; Focal cerebral ischemia; Neuroprotection; Oxygen-glucose deprivation (OGD)