The Finer Aspects of Grid-Walking and Cylinder Tests for Experimental Stroke Recovery Studies in Mice.

The choice of behavioral tests and their proper execution is critically important for experimental and preclinical therapeutic stroke recovery studies, where improvement of impaired neurological function(s) is the main outcome measure. Two tests that focus on spontaneous motor behaviors of the forelimb during gait and exploratory rearing and are expert recommended for stroke recovery studies in mice are grid-walking and cylinder tasks. Both tests have been widely used in various experimental stroke studies to evaluate acute and chronic motor impairment.

A Low-Budget Photothrombotic Rodent Stroke Model.

A number of animal stroke models have been developed and used over the years to study the pathological mechanisms of this disorder and develop new therapies. Among them, the photothrombotic model of ischemic stroke has been central in various studies focusing on understanding of the basic biology of neural repair, identification and validation of key molecular targets involved in post-stroke recovery, and preclinical testing of various therapeutic approaches. To facilitate uniformity among various experimental groups using this expert-recommended mouse model of choice for stroke recovery studies, in this chapter we describe in detail a low-budget technique to induce photothrombosis in the mouse primary motor cortex.

Delayed Exercise-induced Upregulation of Angiogenic Proteins and Recovery of Motor Function after Photothrombotic Stroke in Mice.

Treatments promoting post-stroke functional recovery continue to be an unmet therapeutic problem with physical rehabilitation being the most reproduced intervention in preclinical and clinical studies. Unfortunately, physiotherapy is typically effective at high intensity and early after stroke - requirements that are hardly attainable by stroke survivors. The aim of this study was to directly evaluate and compare the dose-dependent effect of delayed physical rehabilitation (daily 5 h or overnight voluntary wheel running; initiated on post-stroke day 7 and continuing through day 21) on recovery of motor function in the mouse photothrombotic model of ischemic stroke and correlate it with angiogenic potential of the brain.

The Effect of Histone Deacetylase Inhibitors Panobinostat or Entinostat on Motor Recovery in Mice After Ischemic Stroke.

Using rigorous and clinically relevant experimental design and analysis standards, in this study, we investigated the potential of histone deacetylase (HDAC) inhibitors panobinostat and entinostat to enhance recovery of motor function after photothrombotic stroke in male mice. Panobinostat, a pan-HDAC inhibitor, is a FDA-approved drug for certain cancers, whereas entinostat is a class-I HDAC inhibitor in late stage of clinical investigation. The drugs were administered every other day (panobinostat-3 or 10 mg/kg; entinostat-1.

Delayed atomoxetine or fluoxetine treatment coupled with limited voluntary running promotes motor recovery in mice after ischemic stroke.

Currently, there is an unmet need for treatments promoting post-stroke functional recovery. The aim of this study was to evaluate and compare the dose-dependent effect of delayed atomoxetine or fluoxetine therapy (starting on post-stroke day 5), coupled with limited physical exercise (2 hours daily voluntary wheel running; post-stroke days 9 to 42), on motor recovery of adult male mice after photothrombotic stroke. These drugs are selective norepinephrine or serotonin reuptake inhibitors indicated for disorders unrelated to stroke.

Motor deficit in the mouse ferric chloride-induced distal middle cerebral artery occlusion model of stroke.

Ferric chloride-induced distal middle cerebral artery occlusion (MCAO) model of stroke was described in mice several years ago, however it lacked in-depth evaluation of the post-stroke functional outcomes in the animals. In this study, we reproduced the recently developed model and expanded its characterization by thorough evaluation of blood supply, cerebral infarction, and motor function in adult male and female mice up to 14 days after stroke. Our observations indicate near complete interruption of blood flow in the distal MCA shortly after application of 20 % ferric chloride over the artery through a cranial window, which remained occluded for at least 4 h.