Cognitive, neurohistological and mortality outcomes following the four-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion: The impact of diabetes and aging.

Chronic cerebral hypoperfusion (CCH) may be involved in the etiology of aging-related dementias, and several risk factors contribute to their development and/or aggravation. We previously reported on the development of the 4-VO/ICA model of CCH, and the impact of hypertension on the cognitive and histological outcomes of CCH. Here, we advanced those studies by investigating how 4-VO/ICA alone or in combination with diabetes affects survival, body weight and cognitive performance in both young and middle-aged rats. Subsequently, middle-aged rats were examined for the impact of diabetes on CCH-induced neurodegeneration, white matter damage, and glial cells response. Diabetes alone reduced body weight and increased mortality rate slightly in young rats; these effects were striking, however, in the older animals. After CCH alone, neither body weight nor mortality rate changed significantly in both age groups. However, when CCH was combined with diabetes, mortality rate increased significantly in both aged groups. Young rats were cognitively asymptomatic to CCH, but they became 'mildly' impaired after CCH combined with diabetes. In middle-aged rats, CCH severely impaired memory, which was significantly worsened by diabetes. Moreover, diabetes aggravated neurodegeneration in the hippocampus and white matter injury in the corpus callosum and it promoted glial activation in the hippocampus and white matter of CCH middle-aged rats. These data suggest that diabetes interacts synergistically with age and reduces the capacity of the brain to adequately respond to CCH and highlight the importance of associating risk factors in the preclinical investigation of age-related cerebrovascular diseases physiopathology and potential therapies.

Oral glutamine is superior than oral glucose to promote glycemia recovery in mice submitted to insulin-induced hypoglycemia.

The effect of the oral administration of blood glucose precursors on glycemia recovery and liver glucose production in fasted mice subjected to insulin-induced hypoglycemia (IIH) was investigated. IIH was obtained with increasing doses (from 0.5 to 2.0 U·kg(-1)) of intraperitoneal regular insulin where glycemia was evaluated from 0 to 300 min after insulin injection. The dose of 1.0 U·kg(-1) showed the best results, that is, a clear glycemia recovery phase without convulsions or deaths. Thus, this dose was used in all experiments. Afterwards, mice submitted to IIH received orally by gavage: saline (control group), glucose (100 mg·kg(-1)), glycerol (100 mg·kg(-1)), lactate (100 mg·kg(-1)), alanine (100 mg·kg(-1)), or glutamine (100 mg·kg(-1)). It was observed that glutamine was more effective in promoting glycemia recovery if compared with glucose, lactate, glycerol, or alanine. In agreement with these results, the best performance in terms of liver glucose production was obtained when glutamine was used as glucose precursors. These results open perspectives for clinical studies to investigate the impact of oral administration of gluconeogenic amino acids to promote glycemia recovery during hypoglycemia.