Table 2. Studies evaluating the effect of stress on stroke recovery in animals.

Author/Year	Species	No. of animals	Stroke model	Stressor	When initiated	Frequency	Estimated Cohen's da for stroke versus stroke+stress	Duration (minutes)	Conclusion
Faraji et al40	Rat	27	Endothelin-1 (ET-1) induced mini stroke- hippocampus	Restraintb	4-5 days poststroke	Daily for 15 days	Memory test d=1.73	60	Stress and corticosterone reduced the severity of memory impairment and anatomic pathology produced by hippocampal mini stroke.
Faraji et al41	Rat	50	ET-1 induced mini stroke in the hippocampus	Restraint	4-5 days poststroke	Daily for 21 days	d=Insufficient details provided	60	Repeated restraint stress enhanced spatial cognition recovery in rats after focal stroke in the hippocampus.
Faraji et al42	Rat	22	ET-1 induced mini stroke in the hippocampus	Restraint	2-3 days post stroke	Daily for 21 days	Reaching d=4.30	60	Focal stroke in the ventrolateral striatum, and restraint stress acted synergistically to impair motor but not spatial performance in rats.
Jin et al43	Rat	60	Photothrombotic ischemic injury in the sensorimotor cortex	Restraint	1 day poststroke	Daily for 5 days	Beam walking d=3.31	120	Stress after stroke led to increased infarct volume, increased apoptotic cell death, and poorer functional recovery.
Kirkland et al44	Rat	78	Devascularization lesion of the motor cortex	Restraint	Prestress group-15 days prestroke, Post stress gp- 1 day poststroke	Daily for 15 days	Reaching d=1.87	20	Chronic restraint stress before or after stroke, impaired motor recovery and compensation, poststroke stress increased infarct size and edema in rats.
Kirkland et al45	Rat	32	Devascularization lesion of the motor cortex	Restraint	1 day poststroke	Daily for 15 days	Reaching d=1.59	20	Chronic stress and corticosterone treatment impaired motor skill recovery and promoted compensatory movement strategies in a task-specific manner.
Merrett et al46	Rat	29	Devascularization lesion of the motor cortex	Restraint	7 days prestroke	Daily for 28 days	Reaching d=1.29	20	Stress reduced motor function recovery after stroke in rats, with aged rats displaying greater functional impairment.
Wang et al89	Rat	30	Middle cerebral artery occlusion (MCAO)	Chronic mild stress (CMS)- food and water deprivation, 45° cage tilt, overnight illumination, soiled cage, swimming in 4°C water, foot shock, tail pinch, paired caging.	Poststroke time not specified	Day and night for 18 days	Cell survival in dentate gyrus d=11.38	Variable	CMS induced depressive behaviors in rats subjected to stroke and this was accompanied by reduced neurogenesis and altered neurogenic fate by increasing the differentiation of neural progenitor cells to glial lineage cells.
Zucchi et al48	Rat	59	Devascularization lesion of the motor cortex	Restraint/variable (restraint, overcrowding, forced swimming, foot shock, saline injection, shaking, fox odor, social isolation).	7 days pre stroke	Daily for 21 days	Reaching d=0.62	20	Predictable restraint stress led to more pronounced motor impairments than unpredictable variable stress in skilled motor tasks before and after stroke.
Zucchi et al47	Rat	22	Devascularization lesion of the motor cortex	Restraint	7 days pre stroke	Daily for 28 days	Reaching d=1.10	20	Stress induced greater impairment and diminished recovery of motor function, which was related to increased glucocorticoid receptor activation in a rat model.

^aWhere data (means and s.d.) necessary for the calculation of Cohen's d were not explicitly reported in text, they were estimated from the figures provided in the manuscript.

^bRestraint involved animals being placed in a transparent Plexiglass tube (5 to 7.5 cm diameter).