RGD Reference Report - Prophylactic angiotensin type 1 receptor antagonism confers neuroprotection in an aged rat model of postoperative cognitive dysfunction. - Rat Genome Database
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Prophylactic angiotensin type 1 receptor antagonism confers neuroprotection in an aged rat model of postoperative cognitive dysfunction.

Authors: Li, Z  Cao, Y  Li, L  Liang, Y  Tian, X  Mo, N  Liu, Y  Li, M  Chui, D  Guo, X 
Citation: Li Z, etal., Biochem Biophys Res Commun. 2014 Jun 20;449(1):74-80. doi: 10.1016/j.bbrc.2014.04.153. Epub 2014 May 9.
RGD ID: 10047100
Pubmed: (View Article at PubMed) PMID:24814703
DOI: Full-text: DOI:10.1016/j.bbrc.2014.04.153

Postoperative cognitive dysfunction (POCD) is a common geriatric complication, although its exact neuropathogenesis remains elusive. Blockers of the renin-angiotensin system (RAS) ameliorate cognitive deficits in inflammatory brain disorders, with its effects on POCD not yet fully elucidated. The aim of the present study was to investigate regulation of the brain RAS and the effect of angiotensin II receptor type 1 (AT1) inhibition on surgery-induced cognitive impairment in a well-established rat POCD model. We observed upregulation of angiotensin II protein expression and AT1 subtype B transcript levels in the hippocampus after laparotomy, suggesting surgical stress activates the hippocampal RAS in aged rats. Chronic pretreatment with 0.1 mg/kg/day candesartan, an AT1 antagonist, significantly attenuated surgery-induced cognitive deficits in the Morris water maze task without altering blood pressure. Candesartan also decreased hippocampal blood-brain barrier (BBB) permeability. Concomitant with these functional benefits, we observed significant inhibition of hippocampal neuroinflammation, evidenced by decreased glial reactivity and phosphorylation of the NF-kappaB p65 subunit, as well as marked reductions in interleukin-1beta, tumor necrosis factor-alpha, and cyclooxygenase-2. Our results are the first to show that activation of the brain RAS after surgery contributes to POCD in aged rats. Chronic treatment with low doses of candesartan may elicit blood pressure-independent neuroprotective effects in POCD by improving BBB function and promoting resolution of neuroinflammation.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Agtr1a  (angiotensin II receptor, type 1a)
Agtr1b  (angiotensin II receptor, type 1b)

Genes (Mus musculus)
Agtr1a  (angiotensin II receptor, type 1a)
Agtr1b  (angiotensin II receptor, type 1b)

Genes (Homo sapiens)
AGTR1  (angiotensin II receptor type 1)


Additional Information