Behavioural neuroscienceDelayed minocycline treatment reduces long-term functional deficits and histological injury in a rodent model of focal ischemia
Section snippets
Subjects
Forty-five male Sprague–Dawley rats (Vivarium, Memorial University, St. John’s, NL, Canada) weighing approximately 300 g at the time of surgery were housed in pairs in standard Plexiglas cages maintained on a reverse 12-h light/dark cycle. Food and water were freely available, except when food was restricted during behavioral training and assessment (12–15 g per day). Random assignment to treatment groups was performed prior to surgery. Experimental procedures were approved by the Memorial
Drug treatment and surgery effects
Minocycline is an acidic compound and may cause behavioral side effects in treated animals (e.g. lethargy). To examine adverse drug side effects on animal weight and behavior, sham animals were injected with minocycline (S+M) or vehicle (S+V). There was no significant weight loss due to treatment in S+M animals (t(13)=−0.93, P>0.05). Behavior tests showed no differences in S+M and S+V performance (data not shown) so these data were pooled for all analyses (Sham). There was a significant weight
Discussion
The present findings demonstrate robust neuroprotection in minocycline-treated animals one month following focal ischemia. In the cortex there was a trend toward neuroprotection, whereas striatal damage was clearly attenuated by minocycline treatment. Delayed minocycline treatment has been previously shown to reduce cortical and subcortical infarct by 65 and 42% respectively when administered 2 h following middle cerebral artery occlusion (Yrjanheikki et al., 1999), however infarct measures
Conclusions
Delayed treatment with the anti-inflammatory drug minocycline attenuated focal ischemic injury induced by ET-1. In addition there was a reduction in striatal WM injury. Together this translated into improved behavioral outcome. However, the mechanisms of protection provided by minocycline and the conditions under which it is most effective need further elucidation before clinical studies in stroke should be undertaken.
Acknowledgments
The authors thank Sue Evans for technical assistance. Funding for this project was provided by grants from NSERC, the Canadian Stroke Network and the Heart and Stroke Foundations of New Brunswick, and Newfoundland and Labrador awarded to Dale Corbett. Krista Hewlett was the recipient of an NSERC Undergraduate Student Research Award. D.C. holds a Canada Research Chair in Stroke and Neuroplasticity.
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2020, Behavioural Brain ResearchCitation Excerpt :Additionally, it should be noted that in a preliminary experiment a high number of animals died following ET-1 injection into the NAc alone (Supplemental Fig. 6) as occurred in the current study in combination with ET-1 injection into the mPFC. It is unlikely that these deaths were a result of the long duration of surgery, as the surgery procedure took an equal amount of time among all groups, or the dose of ET-1 chosen, as it has been used in other studies without affecting mortality rates [22,42,43]. However, to our knowledge, this is the first study investigating the effects of ET-1 injections into the NAc so it is possible that restricted blood flow in this region results in secondary damage to other regions.