Microglia Activation in the Midbrain of the Human Neonate: The Effect of Perinatal Hypoxic-Ischemic Injury.

Perinatal hypoxia-ischemia (PHI) is a major risk factor for the development of neuropsychiatric deficits later in life. We previously reported that after prolonged PHI, the dopaminergic neurons of the human neonate showed a dramatic reduction of tyrosine hydroxylase (TH) in the substantia nigra, without important signs of neuronal degeneration despite the significant reduction in their cell size. Since microglia activation could precede neuronal death, we now investigated 2 microglia activation markers, ionized calcium-binding adapter molecule 1 (Iba1), and the phagocytosis marker Cd68.

Apoptotic Markers in the Midbrain of the Human Neonate After Perinatal Hypoxic/Ischemic Injury.

Our previous postmortem studies on neonates with neuropathological injury of perinatal hypoxia/ischemia (PHI) showed a dramatic reduction of tyrosine hydroxylase expression (dopamine synthesis enzyme) in substantia nigra (SN) neurons, with reduction of their cellular size. In order to investigate if the above observations represent an early stage of SN degeneration, we immunohistochemically studied the expression of cleaved caspase-3 (CCP3), apoptosis inducing factor (AIF), and DNA fragmentation by using terminal deoxynucleotidyltransferase-mediated dUTP-biotin 3'-end-labeling (TUNEL) technique in the SN of 22 autopsied neonates (corrected age ranging from 34 to 46.5 gestational weeks), in relation to the severity/duration of PHI injury, as estimated by neuropathological criteria.

Perinatal hypoxia as a risk factor for psychopathology later in life: the role of dopamine and neurotrophins.

Brain development is influenced by various prenatal, intrapartum, and postnatal events which may interact with genotype to affect the neural and psychophysiological systems related to emotions, specific cognitive functions (e.g., attention, memory), and language abilities and thereby heighten the risk for psychopathology later in life.

The Effect of Perinatal Hypoxic/Ischemic Injury on Tyrosine Hydroxylase Expression in the Locus Coeruleus of the Human Neonate.

We have previously shown that perinatal hypoxic/ischemic injury (HII) may cause selective vulnerability of the mesencephalic dopaminergic neurons of human neonate. In the present study, we investigated the effect of perinatal HII on the noradrenergic neurons of the locus coeruleus (LC) of the same sample. We studied immunohistochemically the expression of tyrosine hydroxylase (TH, first limiting enzyme for catecholamine synthesis) in LC neurons of 15 autopsied infants (brains collected from the Greek Brain Bank) in relation to the neuropathological changes of acute or chronic HII of the neonatal brain.

Immunohistochemical demonstration of urocortin 1 in Edinger-Westphal nucleus of the human neonate: colocalization with tyrosine hydroxylase under acute perinatal hypoxia.

Perinatal hypoxia could cause long-term disturbances of the dopaminergic (DA) systems, leading to behavioral and/or neurological deficits later in life. Increased expression of tyrosine hydroxylase (TH) was shown in the substantia nigra (SN) and ventral tegmental area (VTA) of human neonates that suffered severe/acute perinatal hypoxic insults, but also in all neurons of the Edinger-Westphal nucleus (EW). Since EW, in humans, contains urocortin 1 (UCN1)/centrally projecting neurons (EWcp), we investigated: (a) the development of UCN1-positive neurons and the possible effect of neonatal hypoxic/ischemic encephalopathy on UCN1 expression and (b) the possible colocalization of UCN1 with TH in neonates with histological signs of acute hypoxic injury.

Vulnerability of the mesencephalic dopaminergic neurons of the human neonate to prolonged perinatal hypoxia: an immunohistochemical study of tyrosine hydroxylase expression in autopsy material.

Experimental studies indicate that hypoxia to the fetus, a common occurrence in many birth complications in humans, results in long-term disturbances of the central dopaminergic (DA) systems that persist in adulthood. Because dysregulation of DA systems is involved in the pathophysiology of many neurological and psychiatric disorders, we investigated the effects of perinatal hypoxia on the mesencephalic DA neurons of the human neonate using immunohistochemistry. We studied the expression of tyrosine hydroxylase (TH), the first and rate-limiting enzyme in catecholamine synthesis, in substantia nigra, and ventral tegmental area of 18 neonates in relation to the age and severity/duration of hypoxic injury estimated by neuropathological criteria.

Increased expression of tyrosine hydroxylase in the supraoptic nucleus of the human neonate under hypoxic conditions: a potential neuropathological marker for prolonged perinatal hypoxia.

The purpose of this study was to determine whether the increased expression of tyrosine hydroxylase (TH), the first and limiting enzyme in catecholamine synthesis in vasopressin (VP) neurons of the human neonate, represents a primary developmental phenomenon or reflects a secondary phenomenon related to the activation of VP systems due to perinatal hypoxia. Using immunohistochemistry, we investigated TH expression in the supraoptic nucleus (SON) of 15 human neonates at autopsy in relation to the age and severity/duration of hypoxic injury that was estimated on the basis of neuropathological criteria. Increased expression of TH was observed selectively in VP-synthesizing neurons of neonates who experienced prolonged perinatal hypoxia; was not related to the age, body weight/percentile, brain weight, or head perimeter of the subjects but depended on the neuropathological grade of the hypoxic injury (p < 0.