Neuroprotective Therapies after Perinatal Hypoxic-Ischemic Brain Injury

Abstract

Hypoxic-ischemic (HI) brain injury is one of the main causes of disabilities in term-born infants. It is the result of a deprivation of oxygen and glucose in the neural tissue. As one of the most important causes of brain damage in the newborn period, the neonatal HI event is a devastating condition that can lead to long-term neurological deficits or even death. The pattern of this injury occurs in two phases, the first one is a primary energy failure related to the HI event and the second phase is an energy failure that takes place some hours later. Injuries that occur in response to these events are often manifested as severe cognitive and motor disturbances over time. Due to difficulties regarding the early diagnosis and treatment of HI injury, there is an increasing need to find effective therapies as new opportunities for the reduction of brain damage and its long term effects. Some of these therapies are focused on prevention of the production of reactive oxygen species, anti-inflammatory effects, anti-apoptotic interventions and in a later stage, the stimulation of neurotrophic properties in the neonatal brain which could be targeted to promote neuronal and oligodendrocyte regeneration.

Ischemic-Reperfusion Injury Increases Matrix Metalloproteinases and Tissue Metalloproteinase Inhibitors in Fetal Sheep Brain

“…We visualized the signals using enhanced chemiluminescence (ECL Prime; GE Healthcare Bio-Sciences, Pittsburgh, PA, USA) before exposure to autoradiographic film (Phenix, Candler, NC, USA). We detected pro-MMP-2, cleaved-MMP-2, MMP-8, MMP-13, TIMP-1, TIMP-2, TIMP-3, TIMP-4, β-actin, and vinculin bands at 72,64,53,54,26,24,26,25,42, and 117 kDa, respectively. Omission of the primary antibodies eliminated the chemiluminescent signals, thereby establishing the specificity of the primary antibodies to detect the specific protein bands.…”

“…Consequently, it is important to understand the effects of different durations of reperfusion after ischemia on brain injury to determine therapeutic strategies that could attenuate the untoward effects of perinatal brain damage [24]. Accumulating evidence suggests that there is an association between BBB dysfunction and changes in MMPs and TIMPs after hypoxic-ischemic brain injury in the neonatal rodent brain [13,25,26].…”

Study of Risk Factors for the Preterm Infants Birth on the Example of Sumy Region

“…Важливою проблемою перинатології та неонатоло-гії є невиношування вагітності, інтенсивна терапія та виходжування недоношених дітей [2,7]. Особ-ливе місце серед цих дітей займають новонаро-джені з дуже малою (1000-1499 г) масою тіла (ДММТ) та надзвичайно малою (500-999 г) масою тіла (НММТ) при народженні.…”

Hyperinsulinism in neonates of diabetic mothers: guardian of the brain?

“…Neonatal hypoxicischemic encephalopathy represents a serious cerebral event occurring around birth with high mortality and neurological morbidity linked to long-term invalidating sequelae [8]. The pathogenic mechanisms underlying neurological damage resulting from neonatal cerebral hypoxia-ischemia prime a cascade of biochemical events leading to cell dysfunction and ultimately to neuronal death through necrosis, apoptosis and autophagia [8][9][10][11]. Glutamate excitotoxicity, oxidative stress and inflammation are considered as the central biochemical mechanisms implicated in the pathophysiology of neuronal death after birth asphyxia brain damage [8][9][10][11].…”

“…The pathogenic mechanisms underlying neurological damage resulting from neonatal cerebral hypoxia-ischemia prime a cascade of biochemical events leading to cell dysfunction and ultimately to neuronal death through necrosis, apoptosis and autophagia [8][9][10][11]. Glutamate excitotoxicity, oxidative stress and inflammation are considered as the central biochemical mechanisms implicated in the pathophysiology of neuronal death after birth asphyxia brain damage [8][9][10][11]. Glutamate is a major excitatory neurotransmitter, widely expressed in the central nervous system (CNS) that is highly toxic to neurons due to its property to cause excitotoxicity that is involved in the mediation of neuronal death [10,11].…”