Histometric changes and cell death in the thalamus after neonatal neocortical injury in the rat

Abstract

Freezing injury to the developing cortical plate results in a neocortical malformation resembling four-layered microgyria. Previous work has demonstrated that following freezing injury to the somatosensory cortex, males (but not females) have more small and fewer large cells in the medial geniculate nucleus. In the first experiment, we examined the effects of induced microgyria to the somatosensory cortex on neuronal numbers, neuronal size, and nuclear volume of three sensory nuclei: ventrobasal complex, dorsal lateral geniculate nucleus, and medial geniculate nucleus. We found that there was a decrease in neuronal number and nuclear volume in ventrobasal complex of microgyric rats when compared with shams, whereas there were no differences in these variables in the dorsal lateral geniculate nucleus or medial geniculate nucleus. We also found that there were more small and fewer large neurons in both ventrobasal complex and medial geniculate nucleus. In experiment 2, we attempted to determine the role of cell death in the thalamus on these histometric measures. We found that cell death peaked within 24 h of the freezing injury and was concentrated mostly in ventrobasal complex. In addition, there was evidence of greater cell death in males at this age. Taken together, these results support the notion that males are more severely affected by early injury to the cerebral cortex than females.Keywords cell death; dorsal lateral geniculate nucleus; medial geniculate nucleus; microgyria; stereology; ventrobasal thalamus Neuronal migration disorders of the cerebral cortex, such as heterotopias, microgyria, porencephaly, and lissencephaly, have been associated with a wide variety of disorders including intractable epilepsy (Meencke and Janz, 1984; Palmini et al., 1991a, b;Crino, 2004), dyslexia (Galaburda and Kemper, 1979;Galaburda et al., 1985), and developmental delay (Barkovich et al., 1988;Barkovich and Raybaud, 2004 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript developed for many of these neuronal migration disorders. Some of these are the result of spontaneous genetic mutations, such as the reeler or scrambler mouse (Caviness et al., 1972;Goffinet, 1984;Sweet et al., 1996;D'Arcangelo et al., 1997;Rice et al., 1998) or the Tish rat (Lee et al., 1997;Chen et al., 2000), whereas others are induced in otherwise normal rodents such as by prenatal injection with methylazoxymethanol (Ferrer et al., 1982;Chevassus-au-Louis et al., 1999) or neurotrophin-4 (Brunstrom et al., 1997.Malformations have also been induced by mechanical disturbances of the cortical plate. Thus, focal collections of neurons in the molecular layer can be induced by puncture wounds at or around birth (Rosen et al., 1992b), and freezing injury to the developing cortical plate induces malformations that resemble human four-layered microgyria (Dvorák and Feit, 1977;Dvorák et al., 1978;Humphreys et al., 1991;Rosen et al., 1992a;Ferrer et al., 1993;Marret et al., 1995). These induced malformations have been used to mod...

Morphometric changes in subcortical structures of the central auditory pathway in mice with bilateral nodular heterotopia

“…These findings are consistent with both clinical observations and rodent models of injury-induced and genetic models of MCD, where impairments in RAP, coupled with a shift in neuronal size distribution toward more small neurons in the MGN, have both been reported relative to controls [36,[48][49][50]52]. Although the present results further support a link between MCD, impaired auditory processing, and alterations in MGN morphology, the precise neural underpinnings of the deficient auditory phenotype as well as the etiology of the thalamic alterations remain unclear.…”

“…Male rats with injury-induced cerebrocortical microgyria (comparable in structure to those found in dyslexic individuals studied by Galaburda et al) also showed impairments in RAP [45][46][47]. Subsequent examination of neuronal size in the MGN of male rats with injury-induced microgyria revealed not only smaller neurons in general, but a shift in the distribution of neuronal sizes toward the left (smaller neurons) compared to sham controls [48][49][50]. Genetic knockdown of the rodent homolog Dyx1c1-a candidate dyslexia risk gene in humans-also have been shown to lead to MCD (e.g., neural ectopias in layer 1 of the cortex, white matter heterotopia; [51][52][53]).…”

“…In actuality, numerous studies have reported structural differences in the brain in relation to sex within clinical and rodent model literature [4,19,[48][49][50][69][70][71][72][73][74]. In an HI injury model, it was found that male HI injured rats showed impairments on a RAP task, while comparably injured females showed similar RAP performance to controls [72,73].…”

Thalamocortical pathway specialization for sound frequency resolution

“…The two pathways may also have distinct developmental sensitivity. Early developmental perturbations alter frequency bandwidth (and resolution) in VAF moreso than in A1, and the effect may ultimately be traced back to developmental change in thalamocortical pathways (Escabi et al, 2007;Higgins et al, 2008;Rosen et al, 2006). Future studies will be needed to determine whether a VAF-specific loss of frequency resolution is associated with pathway-specific restructuring of the MGBv frequency organization described here.…”

Effects of inter-alpha inhibitor proteins on neonatal brain injury: Age, task and treatment dependent neurobehavioral outcomes

“…Excitotoxicity and inflammation leading to neuronal cell death can extend from days to weeks following perinatal brain damage (Ferriero, 2004, Hagberg, et al, 2002, Rosen, et al, 2006, Volpe, 2008, Volpe, 2009). Elevated pro-inflammatory cytokines are major contributors to the onset of inflammation in neonatal HI injury, which may cause and/or accentuate neuronal pathology predisposing neonates to poor neurobehavioral outcomes (Grether, et al, 2003, Leviton, et al, 2011, Nelson, et al, 1998, Szaflarski, et al, 1995, Yoon, et al, 1997, Yoon, et al, 1997, Yoon, et al, 1997).…”