Thrombin preconditioning provides protection in a 6-hydroxydopamine Parkinson's disease model

被引:28
作者
Cannon, JR
Keep, RF
Hua, Y
Richardson, RJ
Schallert, T
Xi, GH
机构
[1] Univ Michigan, Dept Neurosurg, Crosby Neurol Labs, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA
[4] Univ Texas, Dept Psychol, Austin, TX 78712 USA
[5] Univ Texas, Inst Neurosci, Austin, TX 78712 USA
关键词
Parkinson; behavior; preconditioning; thrombin; 6-hydroxydopamine; ventricle;
D O I
10.1016/j.neulet.2004.10.089
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Low-dose thrombin given several days before lesioning is neuroprotective in ischemic and hemorrhagic models of stroke, an effect termed thrombin preconditioning (TPC). Here, the ability of TPC to provide protection in a 6-hydroxydopamine (6-OHDA) model of Parkinson's disease (PD) was evaluated. All animals received 10 mug 6-OHDA into the fight medial forebrain bundle. Three, days prior to 6-ORDA, the animals received either 1 U rat thrombin (n = 17) or saline (n = 14) 1 mm above the site of neurotoxin delivery. The animals were then evaluated for neurobehavioral deficits until 21 days post-injection. TPC animals performed significantly better on both a vibrissae-elicited forelimb placing test and a forelimb-use asymmetry test than the saline controls. The animals were then sacrificed for either catecholamine determination by HPLC with electrochemical detection or for histopathology to determine lateral ventricular volume or striatal tyrosine hydroxylase immunoreactivity. Although TPC did not protect against the dopamine depletion associated with this severe model. it did reduce dopaminergic terminal loss and ventricular enlargement as compared to saline-treated animals. This report presents the new finding that preconditioning (and TPC in particular) provides protection in a 6-OHDA PD model. Understanding the, mechanisms involved in TPC- mediated protection may stimulate innovative therapeutic regimens. (C) 2004 Elsevier Ireland, Ltd. All rights reserved.
引用
收藏
页码:189 / 194
页数:6
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