Soy Protein Diet Preserves Skilled Ladder Rung Walking Performance after Stroke Better than Isoflavones Alone in Adult and Aged Male Rats

Stroke injuries can reduce the ability of patients to perform daily activities like walking, eating, dressing, and other basic functions. Dietary interventions represent potential strategies for reducing the impact of strokes in people identified as being at enhanced risk due to lifestyle, genetics, previous stroke, or other factors. We have previously shown that young animals fed a semi‐purified diet containing soy protein isolate (SPI) experienced less disability after stroke than rats fed a diet containing caseinate (CAS). We hypothesized that the isoflavones daidzein and genistein, the two most abundant phytoestrogens in SPI, were likely mediating the observed benefits. To test this hypothesis, we utilized the same two diets (SPI and CAS) along with a third diet consisting of CAS plus added purified isoflavones daidzein and genistein (CAS + ISO) to match the isoflavone content of the SPI diet. Adult and aged male Long Evans Hooded rats were fed a semi‐purified diet containing either 1) SPI, 2) CAS, or 3) CAS+ISO. After two weeks on diet, rats were introduced to the skilled ladder rung walking task and baseline performance was recorded. Rats then underwent permanent unilateral middle cerebral artery occlusion (MCAO) to induce a stroke lesion (Day 0). After stroke, rats were maintained on the same diet and performance on the skilled ladder rung walking task was repeated on Day +3. At three days after stroke, both adult and aged rats fed the soy protein‐based diet exhibited significantly fewer forelimb slips than rats fed the caseinate‐based diet (p<0.05). This represents a significant reduction in the degree of forelimb impairment in the SPI diet group compared to the CAS diet group. The CAS+ISO diet affected adult and aged rats differently. In adult rats, performance on the walking task (best to worst) was a follows: SPI > CAS+ISO > CAS, but CAS+ISO was not significantly different than SPI or CAS (p>0.05). However, in the aged rats, no benefit of isoflavones was detected, as CAS+ISO and CAS rats exhibited significantly more slips than the SPI rats (p<0.05), and were not different from each other. The current results extend our previous findings that diets containing SPI as the sole protein source provides some protection from neurological damage following stroke in adult and aged rats. Although a portion of the SPI‐mediated neuroprotection in adult rats may be due to isoflavones, the contribution of isoflavones to this neuroprotection may differ between younger and older animals Support or Funding Information NCCIH R15‐RAT006593A; Diet provided by DuPont Nutrition & Health