Offspring of rats with cerebral hypoxia-ischemia manifest cognitive dysfunction in learning and memory abilities

Neonatal hypoxic-ischemic encephalopathy is a serious neurological disease,often resulting in long-term neurodevelopmental disorders among surviving children.However,whether these neurodevelopmental issues can be passed to offspring remains unclear.The right common carotid artery of 7-day-old parental-generation rats was subjected to permanent ligation using a vessel electrocoagulator.Neonatal hypoxic-ischemic rat models were established by subjecting the rats to 8%O2–92%N2 for 2 hours.The results showed that 24 hours after hypoxia and ischemia,pathological damage,cerebral atrophy,liquefaction,and impairment were found,and Zea-Longa scores were significantly increased.The parental-generation rats were propagated at 3 months old,and offspring were obtained.No changes in the overall brain structures of these offspring rats were identified by magnetic resonance imaging.However,the escape latency was longer and the number of platform crossings was reduced among these offspring compared with normal rats.These results indicated that the offspring of hypoxic-ischemic encephalopathy model rats displayed cognitive impairments in learning and memory.This study was approved by the Animal Care&Welfare Committee of Kunming Medical University,China in 2018(approval No.kmmu2019072).

Breviscapine reduces neuronal injury caused by traumatic brain injury insult:partly associated with suppression of interleukin-6 expression

Breviscapine,extracted from the herb Erigeron breviscapus,is widely used for the treatment of cardiovascular diseases,cerebral infarct,and stroke,but its mechanism of action remains unclear.This study established a rat model of traumatic brain injury induced by controlled cortical impact,and injected 75 μg breviscapine via the right lateral ventricle.We found that breviscapine significantly improved neurobehavioral dysfunction at 6 and 9 days after injection.Meanwhile,interleukin-6 expression was markedly down-regulated following breviscapine treatment.Our results suggest that breviscapine is effective in promoting neurological behavior after traumatic brain injury and the underlying molecular mechanism may be associated with the suppression of interleukin-6.

Novel mutations and sequence variants in exons 3-9 of human T Cell Factor-4 gene in sporadic rectal cancer patients stratified by microsatellite instability

AIM: To establish the role of human T Cell Factor-4 (hTCF-4) gene exons 3-9 mutation status in association with sporadic rectal cancer with microsatellite instability (MSI). METHODS: Microsatellite markers were genotyped in 93 sporadic rectal cancer patients. Eleven cases were found to be high-frequency MSI (MSI-H). Sequence analysis of the coding region of the exons 3-9 of hTCF-4 gene was carried out for the 11 MSI-H cases and 10 controls (5 microsatellite stability (MSS) cases and 5 cases with normal mucosa). The sequencing and MSI identification were used. RESULTS: Several novel mutations and variants were revealed. In exon 4, one is a 4-position continuous alteration which caused amino acid change from Q131T and S132I (391insA, 392 G > A, 393 A > G and 395delC) and another nucleotide deletion (395delC) is present in MSI-H cases (5/10 and 4/10, respectively) but completely absent in the controls.CONCLUSION: Novel mutations in exon 4 of hTCF-4 gene were revealed in this study, which might be o importance in the pathogenesis of sporadic rectal cance patients with MSI-H.

Synaptosomal-associated protein 25 may be an intervention target for improving sensory and locomotor functions after spinal cord contusion

Synaptosomal-associated protein 25 k Da（SNAP-25） is localized on the synapse and participates in exocytosis and neurotransmitter release. Decreased expression of SNAP-25 is associated with Alzheimer＇s disease and attention deficit/hyperactivity disorder. However, the expression of SNAP-25 in spinal cord contusion injury is still unclear. We hypothesized that SNAP-25 is associated with sensory and locomotor functions after spinal cord injury. We established rat models of spinal cord contusion injury to detect gene changes with a gene array. A decreased level of SNAP-25 was detected by quantitative real time-polymerase chain reaction and western blot assay at 1, 3, 7, 14 and 28 days post injury. SNAP-25 was localized in the cytoplasm of neurons of the anterior and posterior horns, which are involved in locomotor and sensory functions. Our data suggest that reduced levels of SNAP-25 are associated with sensory and locomotor functions in rats with spinal cord contusion injury.