Table 4.

Splenectomy and stroke outcome in rodents.

Factors Associated with Splenectomy		Time of Splenectomy		Species		Stroke Model		Survival		Outcomes		Beneficial/ Detrimental		Refs.
Pre-stroke splenectomy		14 days before MCAO		male SD rats		pMCAO		48 hours, 96 hours		Decreased infarction volume in the brain (48 hours and 96 hours). Reduced neurodegeneration after ischemic insult, decreased numbers of activated microglia, macrophages and neutrophils present in the brain tissue (96 hours).		Beneficial		[5, 24]
		14 days before MCAO		male SD rats		pMACO		24 hours		Reduce cerebral infarct volumes, Lower numbers of T cells, neutrophils, and macrophages in brain tissue and lower levels of pro-cytokines, but higher levels of IL-10.		Beneficial		[26]
		14 days before MCAO		male SD rats		pMCAO		4 days		Decreased infarct size and the amount of IFNγ in the infarct post-MCAO.		Beneficial		[27]
		14 days before MCAO		Male C57BL/6J mice		tMCAO		1 days, 3 days, 5 days		reduced infarct size (5 days), neurological deficit(1, 3, 5 days) and brain interferon-γ (3 days) after stroke		Beneficial		[19]
		14 days before MCAO		male SD rats		pMCAO		96 hours		Reduced the amount of IP-10 in the infarct area of rats post-MCAO		Beneficial		[67]
		3 days before stroke		male SD rats		intracerebral haemorrhage (ICH)		3 days		significantly decreased edema and brain water content.		Beneficial		[69]
upon stroke splenectomy		Splenectomy just before MCAO		Male C57BL/6J mice		tMCAO 30min		3 days, 7 days		Not reduced infarct volume and swelling.		No effect		[20]
		Splenectomy immediately before MCAO		male SD rats		tMCAO 90min		24, 72, 144 hours		reduced infarct volume(MRI).		Beneficial		[28]
								1 day-7 days		No significant difference between both group behavioral scores at different time points.		No effect
		Splenectomy immediately before MCAO		Male Lewis rats		tMACO 120min		3 and 6 hours		Worse neurological scores		Detrimental		[72]
								72 hours		Similar infarct size in both groups		No effect
								4 weeks		No effect on behavioral outcomes and immune response to myelin basic protein
		Splenectomy right upon reperfusion		Male SD rats		tMCAO 90min		3 days		significantly reduced the infarct size and immune cell infiltration 3d after MCAO,		Beneficial		[29]
								28 days		but fails to reduce brain tissue loss at 28 days after MCAO		No effect
								3-28 days		Result in a transient improvement in functional performance; however, it could not promote long-term functional recovery after MCAO
Post-stroke splenectomy		3 days after MCAO		Male SD rats		tMCAO 90min		5 days, 28 days		Not reduced infarct volume (5 days) and brain tissue loss (28 days).		No effect		[29]
								3-28 days		no effect on sensorimotor function or cognitive function.
Factors Associated with Splenectomy			Time of Splenectomy		Species		Stroke Model		Survival		Outcomes		Beneficial/ Detrimental		Refs.
splenectomy about gender			14 days before MCAO		Male and female C57BL/6J mice		tMCAO 60min		4 days		Decreased infarct size in males,not females.		Beneficial		[73]
splenectomy about age			14 days before MCAO		Older C57BL/6J male mice (18-22 months)		tMCAO 60min		4 days		Improved neurobehavioral and infarct outcomes. Reduced the number of peripheral immune cells infiltrating into the brain and decreased levels of peripheral inflammatory cytokines after stroke.		Beneficial		[30]
			3 days before hypoxia-ischemia (HI)		Postnatal day-7 rats		Neonatal HI		72 hours		Decreased infarct volume.		Beneficial		[71]
									3 weeks		Diminished brain atrophy and Improved behavioral outcome. Improved short- and long-term body weight gain after HI.
Alternative therapy for splenectomy			Splenic irradiation at 3 and 4hrs after the start of ischemia		Male SD rats		tMCAO 120min		48 hours		Reduced cerebral infarct volumes in the rats irradiated at 3 hours		Beneficial		[25]
									7 days		Reduced cerebral infarct volumes and counts of microglia, infiltrating T cells and apoptotic neurons in the rats irradiated at 4 hours
Splenectomy in other treatment model	LPS-preconditioning (LPS-PC)		14 days before MCAO		Male mice		tMCAO 35min		72 hours		Eliminated the neuroprotection of LPS-PC after stroke. Similar large infarcts in both LPS- and saline-treated splenectomized mice.		Detrimental		[46]
	Remote ischemic limb conditioning		Splenectomy and adoptive transfer of CCR2 KO splenocytes into C57BL/6 mice, just before MCAO,		Male and female C57BL/6J mice, CCR2 KO mice		tMCAO 30min		2 months		CCR2-deficient splenocytes transfer abolishes Remote Ischemic Limb Conditioning-mediated protection in splenectomized mice.		Detrimental		[93]
	Remote ischemic precondition (RIPC) of a limb		1 day or 2 weeks before RIPC and MCAO		Male SD rats		tMCAO 90 min		3 days		Reduced the protective effect of RIPC on ischemic brain injury and reversed the effects of RIPC on circulating immune cell composition.		Detrimental		[93]
	Human multipotent adult progenitor cells treatment		14 days before		Male Long Evans rats		tMCAO 90 min		21days, 28 days		Eliminated the improvement of stroke recovery treated with MAPC.		Detrimental		[85]
	Neural stem cell transplantation		3 days before ICH		Male SD rats		ICH		1 day, 3 days		Eliminated the effect of NSCs on brain water content (3 days), perihematomal inflammatory cells (1 day), and initial neurologic deficits (3 days).		Detrimental		[69]