Absolute lymphocyte and neutrophil counts in neonatal ischemic brain injury

Objectives: This study aimed to identify differences in absolute neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio between neonates with two forms of ischemic brain injury, hypoxic-ischemic encephalopathy, and acute ischemic stroke, compared to controls. We also aimed to determine whether this neutrophil/lymphocyte response pattern is associated with disease severity or is a consequence of the effects of total-body cooling, an approved treatment for moderate-to-severe hypoxic-ischemic encephalopathy. Methods: A retrospective chart review of 101 neonates with hypoxic-ischemic encephalopathy + total-body cooling (n = 26), hypoxic-ischemic encephalopathy (n = 12), acute ischemic stroke (n = 15), and transient tachypnea of the newborn (n = 48) was conducted; transient tachypnea of the newborn neonates were used as the control group. Absolute neutrophil count and absolute lymphocyte count at three time-intervals (0–12, 12–36, and 36–60 h after birth) were collected, and neutrophil-to-lymphocyte ratio was calculated. Results: Hypoxic-ischemic encephalopathy + total-body cooling neonates demonstrated significant time-interval-dependent changes in absolute lymphocyte count and neutrophil-to-lymphocyte ratio levels compared to transient tachypnea of the newborn and acute ischemic stroke patients. Pooled analysis of absolute lymphocyte count for neonates with acute ischemic stroke and hypoxic-ischemic encephalopathy (not hypoxic-ischemic encephalopathy + total-body cooling) revealed that absolute lymphocyte count changes occurring at 0–12 h are likely due to disease progression, rather than total-body cooling treatment. Conclusion: These data suggest that the neutrophil/lymphocyte response is modulated following neonatal ischemic brain injury, representing a possible target for therapeutic intervention. However, initial severity of hypoxic-ischemic encephalopathy among these patients could also account for the observed changes in the immune response to injury. Thus, additional work to clarify the contributions of cooling therapy and disease severity to neutrophil/lymphocyte response following hypoxic-ischemic encephalopathy in neonates is warranted.

Targets for Neuroprotection in Ischemic Stroke

Cerebral ischemia or hypoxia-ischemia initiate a cascade of biochemical events including impaired reuptake of glutamate into perisynaptic glia causing glutamate flooding, calcium fluxing through NMDA glutamate channels, activation of neuronal nitric oxide synthetase, and impaired mitochondrial ATP production. In animal models it is possible to block these steps and protect the brain but the temporal window of protection after the insult lasts only a few hours. Recombinant TPA is clinically protective if given within 3 hours of stroke, but other agents have not been shown to protect brain tissue after stroke. However, total body cooling has also been shown to protect the brain of term infants if initiated within 6 hours of perinatal asphyxia, and a similar level of cooling may provide protection for the brain in adults who have been resuscitated after cardiac arrest.