Piracetam improves cognitive deficits caused by chronic cerebral hypoperfusion in rats.
Piracetam is the derivate of gamma-aminobutyric acid, which improves the cognition,memory,consciousness, and is widely applied in the clinical treatment of brain dysfunction. In the present experiments, we study the effects of piracetam on chronic cerebral hypoperfused rats and observe its influence on amino acids, synaptic plasticity in the Perforant path-CA3 pathway and apoptosis in vivo. Cerebral hypoperfusion for 30 days by occlusion of bilateral common carotid arteries induced marked amnesic effects along with neuron damage, including: (1) spatial learning and memory deficits shown by longer escape latency and shorter time spent in the target quadrant; (2) significant neuronal loss and nuclei condensation in the cortex and hippocampus especially in CA1 region; (3) lower induction rate of long term potentiation, overexpression of BAX and P53 protein, and lower content of excitatory and inhibitory amino acids in hippocampus. Oral administration of piracetam (600 mg/kg, once per day for 30 days) markedly improved the memory impairment, increased the amino acid content in hippocampus, and attenuated neuronal damage. The ability of piracetam to attenuate memory deficits and neuronal damage after hypoperfusion may be beneficial in cerebrovascular type dementia.
He
Zhi
Z
Department of Pharmacology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Liao
Yun
Y
Zheng
Min
M
Zeng
Fan-Dian
FD
Guo
Lian-Jun
LJ
D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology*; D004353:Drug Evaluation, Preclinical; D004594:Electrophysiology; D020925:Hypoxia-Ischemia, Brain / Q000150:complications*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010889:Piracetam / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D018696:Neuroprotective Agents; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D010889:Piracetam
Klin Khir (1962). 1993;(7-8):14-7
8139182
Neurol Neurochir Pol. 1997 Nov-Dec;31(6):1101-9
9591298
Zh Nevrol Psikhiatr Im S S Korsakova. 2005;105(1):36-41
15704481
Nature. 1993 Jan 7;361(6407):31-9
8421494
J Neurophysiol. 1998 Apr;79(4):2111-8
9535972
Behav Brain Res. 2001 May;120(2):159-68
11182164
J Physiol. 1973 Jul;232(2):331-56
4727084
Wiad Lek. 1998;51(7-8):321-5
9748886
Dement Geriatr Cogn Disord. 2002;13(4):217-24
12006732
J Neurophysiol. 2002 Feb;87(2):669-78
11826036
Life Sci. 2003 Dec 12;74(4):435-50
14609722
Arch Gerontol Geriatr. 1993 Mar-Apr;16(2):149-64
15374345
Neurobiol Dis. 2003 Jul;13(2):75-88
12828932
Brain Res. 2002 Jun 14;940(1-2):86-94
12020879
Neurochem Int. 2003 Sep-Oct;43(4-5):461-7
12742092
Neuroscience. 2003;118(1):161-77
12676147
J Int Med Res. 1999 Jul-Aug;27(4):201-5
10599034
Brain Res. 2000 Jul 7;870(1-2):157-62
10869513
J Neurosci. 2003 May 1;23(9):3807-19
12736351
Neurochem Int. 1996 Aug;29(2):115-20
8837039
Brain Res. 1995 Mar 6;673(2):290-6
7606443
Acta Pharmacol Sin. 2004 Dec;25(12):1590-6
15569402
J Neurol Sci. 2004 Nov 15;226(1-2):19-23
15537513
Arch Clin Neuropsychol. 2005 Mar;20(2):229-41
15708732
Neurotoxicology. 2002 May;23(1):19-31
12164545
Eur J Pharmacol. 2000 Jun 9;398(1):65-72
10856449
Eur J Pharmacol. 2006 Aug 7;542(1-3):77-83
16806158
Curr Drug Targets CNS Neurol Disord. 2004 Jun;3(3):181-94
15180479
Neuroscience. 1998 Nov;87(1):171-80
9722150
Stroke. 2000 Feb;31(2):347-54
10657404
J Neurol Sci. 2000 Oct 1;179(S 1-2):1-33
11054482
Proc Natl Acad Sci U S A. 1990 Aug;87(15):5832-6
2377621
Zhongguo Yao Li Xue Bao. 1991 Mar;12(2):145-7
1685614
Drugs Aging. 1991 Jan;1(1):17-35
1794001
Zh Nevropatol Psikhiatr Im S S Korsakova. 1983;83(7):984-90
6624331