Effects of pre- and postnatal protein malnutrition in hypoxic–ischemic rats

Abstract

Neonatal hypoxic-ischemic encephalopathy (HI) is a major cause of nervous system damage and neurological morbidity. Perinatal malnutrition affects morphological, biochemical and behavioral aspects of neural development, including pathophysiological cascades of cell death triggered by ischemic events, so modifying resulting brain damage. Female Wistar rats were subjected to protein restriction during pregnancy and lactation (control group: 25% soybean protein; malnourished group: 7%). Seven days after delivery (PND7), their offspring were submitted to unilateral cerebral HI; rats were then tested for sensorimotor (PND7 and PND60) and memory (PND60) functions. Offspring of malnourished mothers showed marked reduction in body weight starting in lactation and persisting during the entire period of observation. There was a greater sensorimotor deficit after HI in malnourished (M) animals, in righting reflex and in home bedding task, indicating an interaction between diet and hypoxia-ischemia. At PND60, HI rats showed impaired performance when compared to controls in training and test sessions of rota-rod task, however there was no effect of malnutrition per se. In the open field, nourished HI (HI-N) presented an increase in crossings number; this effect was not present in HI-M group. Surprisingly, HI-M rats presented a better performance in inhibitory avoidance task and a smaller hemispheric brain damage as compared to HI-N animals. Our data points to a possible metabolic adaptation in hypoxic-ischemic animals receiving protein malnutrition during pregnancy and lactation; apparently we observed a neuroprotective effect of diet, possibly decreasing the brain energy demand, under a hypoxic-ischemic situation.

Neuronal KATP channels mediate hypoxic preconditioning and reduce subsequent neonatal hypoxic–ischemic brain injury

“…In this study, we adapted a number of behavioral tests, including the geotaxis reflex (Sanches et al, 2012), cliff avoidance reaction (Bouslama et al, 2007) and grip test (Liu et al, 2013) to test whether HPC improves motor functional recovery after HI. In addition to the morphological evidence from TTC staining at 24 h and brain histology at 7 days post-HI, we reported that HPC improved functional and behavioral recovery.…”

“…These tests evaluated: 1) geotaxis reflex (Sanches et al, 2012) to evaluate vestibular and/or proprioceptive functions; 2) cliff avoidance reaction (Bouslama et al, 2007) to check for the presence of maladaptive impulsive behavior; and 3) grip ability (Liu et al, 2013) to assess grip force and fatigability. After completion of the tests, mice were deeply anesthetized with isoflurane and their brains were removed and fixed with 4% paraformaldehyde in PBS for immunohistochemical evaluation.…”

Maternal high-fat diet influences outcomes after neonatal hypoxic-ischemic brain injury in rodents

“…We also considered protein adequacy, since protein malnutrition during pregnancy and lactation results in impaired sensorimotor function after neonatal cerebral hypoxia ischemia. 51 In both groups of pups, weight gain was the same (Table 2), as was serum protein. Although blood glucose was higher in HF progeny at P35, this was not the case at P14; moreover, hyperglycemia reportedly does not increase the severity of hypoxic-ischemic damage in the neonatal rodent brain.…”

Effects of mGluR5 positive and negative allosteric modulators on brain damage evoked by hypoxia-ischemia in neonatal rats

“…Brain damage was reflected by a deficit in the wet weight of the ipsilateral (left) ischemic hemisphere and is expressed as a percentage of the wet weight of the contralateral (right) control hemisphere [19,20]. This method of assessing the developing brain damage in a rat model of HI has recently been used by a number of other research groups [8,17,30]. Our previous control experiments demonstrated equal weight of the left and right hemisphere in naive and sham-operated animals and that H-I induction in 7-day-old rats does not interfere with the mass of the contralateral (reference) hemisphere.…”