Neuroprotective Effect of Necrostain-1 on White Matter Damage in Premature infants

Background: Periventricular white matter damage (PWMD), a common severe disease of the CNS in premature infant, is characterized by the highly mortality and severe sequel. Recent research shows that inflammation play an important role in secondary brain damage after WMD, and is closely related to the occurrence of sequelae and degree of illness. Previous studies have shown that Necrostain-1 has been shown to inhibit programmed cell death and play a protective role in reducing inflammatory response after injury.

Objective: To investigate the effect of Necrostain-1 on animals with white matter injury.

Methods: Take some Sprague Dawley rates which are 3 days after birth, and randomly divided into three groups: the normal control, WMD and WMD +Necrostain-1. Necrostain-1 was injected into the lateral ventricle at 24h after constructing the model of WMD. Immunohistochemistry was used to detect the activation level of microglia and the survival of oligodendrocytes at 3d, 7d, 14d and 21d after modeling. The expression levels of inflammatory factors such as IL-1β, IL-6, and TNF-α were detected by ELISA. Open field test, suspension test and dark avoidance test were used to evaluate the cognitive, behavior and memory abilities of them after 28 days.

Results: 1. Necrostain-1 can slow down the activation of microglia, and attenuated oligodendrocytes death; 2.The results of ELISA showed that Necrostain-1 inhibited the expression of IL-1β, IL-6, and TNF-α. Ethological test revealed that Necrostain-1 had a protective effect on cognition and memory functions.

Conclusion: Necrostain-1 plays a neuroprotective role in rats with white matter injury, which is associated with the suppression of inflammatory responses and apoptosis. This study suggests that Necrostain-1 is a promising therapeutic agent for the treatment of white matter injury in premature infants.