Abstract
Objective: To determine whether the anti-inflammatory effects of leukemia inhibitory factor (LIF) are altered in aged male and female rats.
Methods: Focal ischemia was induced in 3 month old male and 18 month old male/female Sprague-Dawley using the middle cerebral artery occlusion (MCAO) procedure. Animals were treated with PBS or LIF at 6, 24, and 48 h after MCAO (125 µg/kg). Infarct volume in aged animals was quantified with T2-weighted MRI. Functional motor skills were assessed immediately prior to euthanization at 72 h post-MCAO. Protein levels of CD11b and IL-12 p40 in brain and spleen tissue were measured using immunoblotting.
Results: At 72 h, there was a trend towards decreased infarct volume in aged female LIF-treated rats compared to female PBS-treated rats. However, there was no decrease in mean infarct volume in the LIF-treated aged male rats compared to PBS-treated aged males. LIF-treated aged female rats showed significant decreases in circling (p<0.05) and significant increase in paw extension (p<0.01) compared to the PBS-treated aged females. Aged male rats treated with LIF did not demonstrate functional recovery compared to their PBS-treated counterparts. Normalized CD11b levels were significantly in LIF-treated young males compared to PBS-treated young males (p<0.05). Although aged male and female animals had lower normalized levels of CD11b in the brain 72 h post-MCAO compared to young males, LIF had no effect on brain CD11b levels in aged rats. LIF increased spleen size (p<0.0001) and splenic CD11b levels (p<0.05) compared to PBS-treated females and there was a significant positive correlation between these two factors in the aged female rats (p<0.05). Furthermore, IL-12 p40 levels in splenic tissue were significantly higher in young male PBS-treated rats compared to aged male (p<0.01) and female rats ((p<0.01). LIF treatment reduced IL-12 p40 levels in the spleen in young rats (p<0.05) but not in either of the aged rat groups.
Conclusions: LIF is more effective at decreasing splenic IL-12 expression and immune cell infiltration in young rats compared to aged rats. However, LIF counteracts the post-stroke splenic response in aged females but not aged male rats.
