Minocycline reduces astrocytic reactivation and neuroinflammation in the hippocampus of a vascular cognitive impairment rat model.
OBJECTIVE
To study the neuroprotective mechanism of minocycline against vascular cognitive impairment after cerebral ischemia.


METHODS
The rat model with vascular cognitive impairment was established by permanent bilateral common carotid artery occlusion (BCCAO). The observing time-points were determined at 4, 8 and 16 weeks after BCCAO. Animals were randomly divided into sham-operated group (n = 6), model group (subdivided into 3 groups: 4 weeks after BCCAO, n = 6; 8 weeks after BCCAO, n = 6; and 16 weeks after BCCAO, n = 6), and minocycline group (subdivided into 3 groups: 4 weeks after BCCAO, n = 6; 8 weeks after BCCAO, n = 6; and 16 weeks after BCCAO, n = 6). Minocycline was administered by douche via stomach after BCCAO until sacrifice. Glial fibrillary acidic protein (GFAP) was examined by Western blotting and immunohistochemistry. Levels of cyclooxygenase-2 (COX-2) and nuclear factor-kappaB (NF-kappaB) were measured by immunohistochemistry. IL-1beta and TNF-alpha levels were tested with ELISA method.


RESULTS
Levels of GFAP, COX-2, NF-kappaB, IL-1beta and TNF-alpha were all up-regulated after permanent BCCAO, which could be significantly inhibited by minocycline.


CONCLUSIONS
Minocycline could ameliorate the inflammation and oxidative stress in the hippocampus of the vascular cognitive impairment rat model.
Cai
Zhi-You
ZY
Department of Neurology, Anhui Medical University, Lu'an 237005, China.
Yan
Yong
Y
Chen
Ran
R
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D002340:Carotid Artery Diseases / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D017536:Carotid Artery, Common; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D053583:Interleukin-1beta / Q000378:metabolism; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D016328:NF-kappa B; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D008911:Minocycline