ABSTRACT
Objective To investigate the effect of persistent hypoglycemia on the cerebral oxidative stress and matrix metalloproteinase-2 (MMP-2) activity of newborn rats and to explore the potential mechanism of hypoglycemia-induced brain injury of newborn.MethodsSeven-day-old rats were injected insulin subcutaneously to induce persistent hypoglycemia.Cerebral cortex,hippocampus and thalamus were collected after 36 hours' observation and stored in -80 ℃.Glutathione (GSH)and glutathione disulfide (GSSG) were detected by commercial kit and GSSG/GSH was calculated.MMP-2 activity was detected by gelatin zymography. The data were analyzed by t test,one or two-wayanalysis of variance and Pearson correlation analysis.Six rats were set as the normal glucose group. ResultsThirty-six hours after induction of hypoglycemia, the cerebral GSSG and GSSG/GSH of hypoglycemic pups elevated about 1.5 times higher than those of control group [GSSG:(15.89 ± 5.46) vs (6.15 ± 3.42) mg/g protein,t =3.704,P =0.004; GSSG/GSH:(5.58± 1.79) ％ vs (2.79±1.76) ％,t =2.712,P=0.022].The GSSG and GSSG/GSH in thalamus of hypoglycemia were significantly higher than those of control [GSSG:(15.93 ± 5.75) mg/g protein vs (5.03±5.14)mg/g protein,P＜0.05; GSSG/GSH:(6.50±3.25) ％ vs (2.41±3.12) ％,P＜0.05],whereas there were no significant differences in the cortex ard hippocampus.The total MMP-2 activity of hypoglycemic animals (2.22±0.59) was significantly higher than that of control (1.21± 0.17)(t=4.064,P=0.002),and significant differences were found between the two groups in cortex (2.14 ± 0.5 vs 1.17± 0.27),hippocampus (2.31± 0.72 vs 1.22 ± 0.37) and thalamus (2.22±0.68 vs 1.24±0.18) with all P＜0.01].The activity of MMP-2 was positively related to GSSG (r=0.575,P=0.0002) and GSSG/GSH (r=0.484,P=0.0003).ConclusionsOxidative stress might play an important role in the persistent hypoglycemia induced brain injury of 7-day-old rat pups and thalamus might be most vulnerable to hypoglycemia.Hypoglycemia might also elevate MMP-2 activity which is positively related to GSSG level and GSSG/GSH of the brain.
ABSTRACT
El hiperinsulinismo congénito (HC) es la causa más común de hipoglicemia persistente en el primer año de vida. Se acompaña de riesgo elevado de daño neurológico irreversible. En los últimos años se ha profundizado en el conocimiento sobre su patogenia, destacándose la heterogenicidad clínica, histológica y genética, con claras implicancias en el diagnóstico y tratamiento. Se describe el caso de un lactante portador de HC que debuta con hipoglicemias sintomáticas a los 5 meses de vida. El objetivo de esta comunicación es, a la luz de los conocimientos actuales, analizar los criterios diagnósticos y terapéuticos de esta patología. Se destaca la importancia de aplicar un algoritmo para guiar el estudio paraclínico y descartar las etiologías más frecuentes asociadas con la hipoglicemia.
Congenital hyperinsulinism (HC) is the most common etiology of persistent hypoglycemia in infants. It is associated with a high risk of irreversible neurological damage. Knowledge about its pathogenesis has improved in the past few years. It is characterized by a heterogeneous clinical presentation, histology and genetic which leads to special diagnosis and treatment features. This is a case report of a 5 month old with HC who had symptomatic hypoglycemia. The objective of this communication is to analyze the diagnosis and treatment criteria of HC. The need to follow a clinical and laboratory guideline for diagnosis will help exclude other causes of hypoglycemia.