Correlation Between Clinical and Histologic Findings in the Human Neonatal Hippocampus After Perinatal Asphyxia

Abstract

Hypoxic ischemic encephalopathy after perinatal asphyxia is a major cause of mortality and morbidity in infants. Here, we evaluated pathologic changes in the hippocampi of a cohort of 16 deceased full-term asphyxiated infants who died from January 2000 to January 2009. Histochemical and immunocytochemical results for glial and neuronal cells were compared between cases with or without seizures and to adult and sudden infant death syndrome cases (n = 3 each). All asphyxiated infants displayed neuronal cell damage and reactive glial changes. Strong aquaporin-4 immunoreactivity was seen on astroglial cells within hippocampi in 50% of cases. In patients with seizures, the expression of metabotropic glutamate receptors was increased in glial cells. Cases with seizures displayed increased microglial activation and greater expression of the inflammatory markers interleukin 1β and complement 1q compared with those in cases without seizures. All cases with seizures displayed alterations in the blood-brain barrier, as assessed by immunohistochemistry for albumin. These findings confirm the complex cascade of cellular and molecular changes occurring in the human neonatal hippocampus after perinatal asphyxia. These changes may contribute to seizure development leading to secondary brain damage. These data may aid in the development of therapeutic targets for neonatal seizures.

Systemic and transdermal melatonin administration prevents neuropathology in response to perinatal asphyxia in newborn lambs

“…This neuroinflammatory response is well described in animal models of perinatal asphyxia, commencing almost immediately after insult and manifesting over days to weeks and acting as a principal mediator of neuronal injury . Similarly, microglial activation and cytokine release are observed over the same timescale in human infants after perinatal asphyxia . MLT administration (IV and transdermal patch) prevented the neuroinflammatory response following asphyxia, with undetectable levels of IL‐1B in CSF and a total reduction in the number of activated microglia within brain regions of interest.…”

“…[57][58][59] Similarly, microglial activation and cytokine release are observed over the same timescale in human infants after perinatal asphyxia. 60,61 MLT administration (IV and transdermal patch) prevented the neuroinflammatory response following asphyxia, with undetectable levels of IL-1B in CSF and a total reduction in the number of activated microglia within brain regions of interest. These results add critical weight to evidence that the antioxidant and anti-inflammatory actions of MLT are central to its neuroprotective benefits, which in turn rescue functional development following birth asphyxia.…”

The Role of Diffusion Tensor Imaging in Detecting Hippocampal Injury Following Neonatal Hypoxic‐Ischemic Encephalopathy

“…[11][12][13][14][15] Hippocampal involvement is commonly found in pathological specimens from neonates who have died of HIE. 16 Hippocampal injury is observed on conventional MR imaging when other signs of severe injury are also apparent. [17][18][19][20] However, limited data exist on the use of DTI to examine the degree of hippocampal injury in HIE and its subsequent implications for prognostication and clinical management.…”

Blood biomarkers for evaluation of perinatal encephalopathy: state of the art

“…In 16 deceased full term asphyxiated infants there was increased expression of IL-1β in the hippocampus in those with seizures, and all cases with seizures displayed alteration in the blood-brain barrier as assessed by immunohistochemistry for albumin (Schiering et al, 2014). The authors speculated that seizure development may lead to secondary brain damage, and that IL-1β may aid in the development of therapeutic targets for neonatal seizures (Schiering et al, 2014).…”