Functional reorganization of the forepaw cortical representation immediately after thoracic spinal cord hemisection in rats.

Spinal cord injury may produce long-term reorganization of cortical circuits. Little is known, however, about the early neurophysiological changes occurring immediately after injury. On the one hand, complete thoracic spinal cord transection of the spinal cord immediately decreases the level of cortical spontaneous activity and increases the cortical responses to stimuli delivered to the forepaw, above the level of the lesion. On the other hand, a thoracic spinal cord hemisection produces an immediate cortical hyperexcitability in response to preserved spinothalamic inputs from stimuli delivered to the hindpaw, below the level of the lesion. Here we show that a thoracic spinal cord hemisection also produces a bilateral increase of the responses evoked in the forepaw cortex by forepaw stimuli, associated with a bilateral decrease of cortical spontaneous activity. Importantly, the increased cortical forepaw responses are immediate in the cortex contralateral to the hemisection (significant within 30min after injury), but they are progressive in the cortex ipsilateral to the hemisection (reaching significance only 2.5h after injury). Conversely, the decreased cortical spontaneous activity is progressive both ipsilaterally and contralaterally to the hemisection (again reaching significance only 2.5h after injury). In synthesis, the present work reports a functional reorganization of the forepaw cortical representation immediately after thoracic spinal cord hemisection, which is likely important to fully understand the mechanisms underlying long-term cortical reorganization after incomplete spinal cord injuries.

Estradiol synthesis within the human brain.

Estradiol biosynthesis is catalyzed by the enzyme aromatase, the product of the CYP19A1 gene. Aromatase is expressed in the brain, where it is involved not only in the control of neuroendocrine events and reproduction, but also in the regulation of neural development, synaptic plasticity and cell survival. In this review we summarize the existing data related with the detection of aromatase in human brain, with particular emphasis in the so-called "non-primary reproductive" areas. Besides hypothalamus, amygdala and preoptic/septal areas, aromatase is expressed in certain regions of basal forebrain, cerebral cortex, hippocampus, thalamus, cerebellum and brainstem of the human brain. Aromatase in human brain is produced by neurons, but there is also an astrocyte subpopulation that constitutively expresses the enzyme. The use of different methodological approaches, including the in vivo analysis by positron emission tomography of human subjects, has permitted to draw a general map of human brain aromatase, but the detailed distribution map is still far to be completed. On the other hand, despite the fact that there is only one aromatase protein, there are multiple mRNA transcripts that differ in the 5'-untranslated region, where regulatory elements reside. To date, some of the aromatase transcripts characteristic of cerebral cortex, as well as of human cell lines of neural origin, have been identified. This characteristic may confer tissue or even region-specific regulation of the expression and therefore it is conceivable to develop selective aromatase modulators to regulate the expression of the enzyme in the human brain. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

Cortical hyperexcitability in response to preserved spinothalamic inputs immediately after spinal cord hemisection.

Chronic injury of the main somatosensory pathways ascending along the spinal cord - the dorsal columns and the spinothalamic tract - can produce both changes in the organization of cortical somatotopic maps and neuropathic pain. Little is known, however, about the early neurophysiological changes occurring immediately after injury. We bilaterally recorded the neural activity of the hindpaw representation of the primary somatosensory cortex evoked by stimuli delivered to the hindpaws before and immediately after a thoracic spinal cord hemisection in anesthetized rats. This unilateral spinal cord injury allowed us to separately investigate the cortical effects of deafferenting the dorsal column (stimuli ipsilateral to the hemisection) or the spinothalamic tract (stimuli contralateral to the hemisection). The hemisection produced immediate bilateral changes in the cortical responses evoked by stimuli delivered to the hindpaw ipsilateral to the hemisection (deafferented dorsal column): an expected loss of classical short-latency cortical responses, accompanied by an unexpected appearance of long-latency activations. At the population level, these activations reflected a progressive stimulus-induced transition of the hindpaw somatosensory cortex from up-and-down states to a sustained activated state. At the single-cell level, these cortical activations resembled the "wind-up" typically observed - with the same type of stimuli - in the dorsal horn cells originating the spinothalamic tract. Virtually no changes were observed in the responses evoked by stimuli delivered to the hindpaw contralateral to the hemisection (deafferented spinothalamic tract). These results suggest that spinal cord hemisection immediately produces an abnormal hyperexcitability of the primary somatosensory cortex in response to preserved spinothalamic inputs from the hindpaw. This immediate cortical hyperexcitability could be important to understand the long-term development of cortical reorganization and neuropathic pain after incomplete spinal cord lesions.

Aromatase expression in the human temporal cortex.

The expression of the human cyp19 gene, encoding P450 aromatase, the key enzyme for estrogen biosynthesis, involves alternative splicing of multiple forms of exon I regulated by different promoters. Aromatase expression has been detected in the human cerebral cortex, although the precise cellular distribution and promoter regulation are not fully characterized. We examined the variants of exon I of cyp19 by PCR analysis and the cellular distribution of the enzyme using immunohistochemistry in the human temporal cortex. We detected four different variants of exon I, suggesting a complex regulation of cyp19 in the cerebral cortex. In addition, the enzyme was localized mainly in a large subpopulation of pyramidal neurons and in a subpopulation of astrocytes. However, the majority of GABAergic interneurons identified by their expression of the calcium-binding proteins calbindin, calretinin and parvalbumin, did not display aromatase immunoreactivity. The broad range of potential modulators of the cyp19 gene in the cortex and the widespread expression of the protein in specific neuronal and glial subpopulations suggest that local estrogen formation may play an important role in human cortical function.