The study provides an instructive animal model of IVH with evidence of acute brain injuries that can be used to evaluate strategies in prevention of IVH and acute posthemorrhagic complications.

Pelizaeus Merzbacher disease is an X-linked dysmyelinating disorder of the CNS, resulting from mutations in the proteolipid protein (PLP) gene. An animal model for this disorder, the myelin-deficient (MD) rat, carries a point mutation in the PLP gene and exhibits a phenotype similar to the fatal, connatal disease, including extensive dysmyelination, tremors, ataxia, and death at approximately postnatal day 21 (P21). We postulated that early death might result from disruption of myelinated neural pathways in the caudal brainstem and altered ventilatory response to oxygen deprivation or hypercapnic stimulus. Using barometric plethysmography to measure respiratory function, we found that the MD rat develops lethal hypoxic depression of breathing at P21, but hypercapnic ventilatory response is normal. Histologic examination of the caudal brainstem in the MD rat at this age showed extensive dysmyelination and downregulation of NMDA and to a lesser extent GABA(A) receptors on neurons in the nucleus tractus solitarius, hypoglossal nucleus, and dorsal motor nucleus of the vagus. Unexpectedly, immunoreactive PLP/DM20 was detected in neurons in the caudal brainstem. Not all biosynthetic functions and structural elements were altered in these neurons, because phosphorylated and nonphosphorylated neurofilament and choline acetyltransferase expression were comparable between MD and wild-type rats. These findings suggest that PLP is expressed in neurons in the developing brainstem and that PLP gene mutation can selectively disrupt central processing of afferent neural input from peripheral chemoreceptors, leaving the central chemosensory system for hypercapnia intact.

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Disorders of sexual differentiation such as androgen insensitivity and gonadal dysgenesis can involve an intrinsic fluidity at different levels, from the anatomical and biological to the social (gender) that must be considered in the context of social constraints. Sex assignment models based on George Engel’s biopsychosocial aspects model of biology accept fluidity of gender as a central concept and therefore help establish expectations within the uncertainty of sex assignment and anticipate potential changes. The biology underlying the fluidity inherent to these disorders should be presented to parents at diagnosis, an approach that the gender medicine field should embrace as good practice. Greek mythology provides many accepted archetypes of change, and the ancient Greek appreciation of metamorphosis can be used as context with these patients. Our goal is to inform expertise and optimal approaches, knowing that this fluidity may eventually necessitate sex reassignment. Physicians should provide sex assignment education based on different components of sexual differentiation, prepare parents for future hormone-triggered changes in their children, and establish a sex-assignment algorithm.