Sulforaphane Protects Piglet Brains from Neonatal Hypoxic-Ischemic Injury

The striatal, primary sensorimotor cortical, and thalamic neurons are highly vulnerable to hypoxia-ischemia (HI) in term newborns. In a piglet model of HI that exhibits similar selective regional vulnerability, we tested the hypothesis that early treatment with sulforaphane, an activator of the Nrf2 transcription factor, protects vulnerable neurons from HI injury. Anesthetized piglets (aged 3–7 days) were subjected to 45 min of hypoxia and 7 min of airway occlusion. At 15 min after resuscitation, the piglets received intravenous vehicle or sulforaphane. At 4 days of recovery, the density of viable neurons in the putamen of vehicle-treated piglets was 31 ± 34% (±SD) that of sham-operated controls. Treatment with sulforaphane significantly increased viability to 77 ± 31%. In the sensorimotor cortex, neuronal viability was also increased; it was 59 ± 35% in the vehicle-treated and 89 ± 15% in the sulforaphane-treated animals. Treatment with sulforaphane increased the nuclear Nrf2 and γ-glu­tamylcysteine synthetase expression at 6 h of recovery in these regions. We conclude that systemic administration of sulforaphane 15 min after HI can induce the translocation of Nrf2 to the nucleus, increase expression of an enzyme involved in glutathione synthesis, and salvage neurons in the highly vulnerable putamen and sensorimotor cortex in a large-animal model of HI. Therefore, targeting Nrf2 activation soon after recovery from HI is a feasible approach for neuroprotection in the newborn brain.

Does the size of the femoral head correlate with the incidence of avascular necrosis of the proximal femoral epiphysis in children with developmental dysplasia of the hip treated by closed reduction?

Purpose The purpose of this study was to identify if any correlation between size of the proximal femoral epiphysis and avascular necrosis (AVN) exists. Methods We retrospectively reviewed 111 patients with developmental dysplasia of the hip treated by closed reduction (124 hips). The diameter and height of both femoral head and ossific nucleus were assessed on preoperative MRI. Results The diameter and the height of the femoral head as well as of the ossific nucleus of the contralateral side were significantly greater than the dislocated side. AVN occurred in 21 (16.9%) out of 124 hips. The rate of AVN gradually decreased with age: 30.0% at six to 12 months, 18.2% at 12 to 18 months and 3.7% at 18 to 24 months. Spearman correlation analysis showed that age is negatively correlated with the incidence of AVN (r = -0.274; p = 0.002) and the diameter of the femoral head has a significantly negative association with the incidence of AVN (r = -0.287; p = 0.001). No significant association was observed between the incidence of AVN and height of the femoral head or size of the ossific nucleus. Hips with AVN were significantly smaller than hips without AVN. Conclusions The size of both the femoral head and the ossific nucleus increase with age although the dislocated femoral head is smaller compared with the contralateral side. The diameter of the femoral head and not the size of the ossific nucleus negatively correlate with the risk of AVN, with a bigger femoral head showing lower risk of AVN. Level of evidence III

Behavioral, biochemical and morphological characteristics of experimentally changed thyroid status of female mice C3H-A

The purpose of the paper was to study changes in neurogenesis and functional state of the central nervous system in female mice С3Н-А predisposed to hormone-dependent tumors in experimental hypo- and hyperthyroidism. Methods. Experimental hyperthyroidism was modeled by intraperitoneal administration of L-thyroxine 50 ug/day and hypothyroidism by oral administration of propylthiouracil 0.4 mg/day for 40 weeks to female mice С3Н-А. Results. Chronic hypo- and hyperthyroidism was characterized by motor (motility) and emotional disorders in mice beginning with 18 day of the experiment, with preferable increase of quantitative indexes of all component of explorative activity and grooming in hyperthyroid mice and disturbance of explorative activity (decrease of hole reflex) in hypothyroid animals. Behavioral disorders was increasing progressively within the experiment (till 40 weeks). In hyperthyroid mice, the dopamine level in the cortex and hippocampus was elevated and in hypothyroid animals, the level and turnover of serotonin was reduced in the same structures of the brain. The changes in thyroid status of С3Н-А mice (hypo- and hyperthyroidism) effected on expression of neurogenesis and angiogenesis factors contradirectory. In hypothyroidism, the expression of GFAP and VEGF was reduced preferably with elevation of expression of PDGFR-α in the neocortex and hippocampus, and in hyperthyroidism, on the contrary, the expression of GFAP and VEGF was increased with decrease of PDGFR-α expressionin the same structures of the brain. In the cortex of С3Н-А mice with hyperthyroidism, the stable structural signs of strengthening the protein synthesized activity in the cytoplasm was observed, that was appeared with reduction of heterochromatin density in the nucleus, increase of polysomes number and hypertrophy of Golgi complex. At the same time, there were mediate signs of destruction of myelin fibers and disturbances in axon-spine synapses, capillarostasis and signs of dystrophic changes of endotheliocytes and perivascular space. In hypothyroidism, disorders involved myelin fibers preferably, spine apparatus and only slight changes of presynaptic terminals. Conclusion. Therefore, it is concluded on the base of behavioral, biochemical and morphological characteristics that hypothyroidism can provoke depressive state development. (For citation: Kozyrko EV, Glushakov PI, Shabanov PD. Behavioral, biochemical and morphological characteristics of experimentally changed thyroid status of female mice C3H-A. Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(1):43-53. doi: 10.17816/RCF16143-53).