Experimental neurology
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Experimental neurology · Aug 2014
Review Comparative StudyIs neuroinflammation in the injured spinal cord different than in the brain? Examining intrinsic differences between the brain and spinal cord.
The field of neuroimmunology is rapidly advancing. There is a growing appreciation for heterogeneity, both in inflammatory composition and region-specific inflammatory responses. This understanding underscores the importance of developing targeted immunomodulatory therapies for treating neurological disorders. ⋯ The question therefore remains as to whether inflammatory cells responding to spinal cord vs. brain injury adopt similar functions and are therefore amenable to common therapies. In this review, we address this question while revisiting and modernizing the conclusions from publications that have directly compared inflammation across brain and spinal cord injuries. By examining molecular differences, anatomical variations, and inflammatory cell phenotypes between the injured brain and spinal cord, we provide insight into how neuroinflammation relates to neurotrauma and into fundamental differences between the brain and spinal cord.
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Experimental neurology · Aug 2014
ReviewThe paradox of chronic neuroinflammation, systemic immune suppression, autoimmunity after traumatic chronic spinal cord injury.
During the transition from acute to chronic stages of recovery after spinal cord injury (SCI), there is an evolving state of immunologic dysfunction that exacerbates the problems associated with the more clinically obvious neurologic deficits. Since injury directly affects cells embedded within the "immune privileged/specialized" milieu of the spinal cord, maladaptive or inefficient responses are likely to occur. Collectively, these responses qualify as part of the continuum of "SCI disease" and are important therapeutic targets to improve neural repair and neurological outcome. ⋯ Here, we consider this interplay during the progression from acute to chronic SCI. Specifically, we survey impaired/non-resolving intraspinal inflammation and the paradox of systemic inflammatory responses in the context of ongoing chronic immune suppression and autoimmunity. The concepts of systemic inflammatory response syndrome (SIRS), compensatory anti-inflammatory response syndrome (CARS) and "neurogenic" spinal cord injury-induced immune depression syndrome (SCI-IDS) are discussed as determinants of impaired "host-defense" and trauma-induced autoimmunity.
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Experimental neurology · Aug 2014
ReviewNeuroinflammatory contributions to pain after SCI: roles for central glial mechanisms and nociceptor-mediated host defense.
Neuropathic pain after spinal cord injury (SCI) is common, often intractable, and can be severely debilitating. A number of mechanisms have been proposed for this pain, which are discussed briefly, along with methods for revealing SCI pain in animal models, such as the recently applied conditioned place preference test. During the last decade, studies of animal models have shown that both central neuroinflammation and behavioral hypersensitivity (indirect reflex measures of pain) persist chronically after SCI. ⋯ Nociceptor activity is known to drive central neuroinflammation in peripheral injury models, and nociceptors appear to be an integral component of host defense. Thus, emerging results suggest that spinal and systemic effects of SCI can activate nociceptor-mediated host defense responses that interact via neuroinflammatory signaling with complex central consequences of SCI to drive chronic pain. This broader view of SCI-induced neuroinflammation suggests new targets, and additional complications, for efforts to develop effective treatments for neuropathic SCI pain.
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Experimental neurology · Jul 2014
Impairment of GABA release in the hippocampus at the time of the first spontaneous seizure in the pilocarpine model of temporal lobe epilepsy.
The alterations in GABA release have not yet been systematically measured along the natural course of temporal lobe epilepsy. In this work, we analyzed GABA extracellular concentrations (using in vivo microdialysis under basal and high K(+)-evoked conditions) and loss of two GABA interneuron populations (parvalbumin and somatostatin neurons) in the ventral hippocampus at different time-points after pilocarpine-induced status epilepticus in the rat, i.e. during development and progression of epilepsy. We found that (i) during the latent period between the epileptogenic insult, status epilepticus, and the first spontaneous seizure, basal GABA outflow was reduced to about one third of control values while the number of parvalbumin-positive cells was reduced by about 50% and that of somatostatin-positive cells by about 25%; nonetheless, high K(+) stimulation increased extracellular GABA in a proportionally greater manner during latency than under control conditions; (ii) at the time of the first spontaneous seizure (i.e., when the diagnosis of epilepsy is made in humans) this increased responsiveness to stimulation disappeared, i.e. there was no longer any compensation for GABA cell loss; (iii) thereafter, this dysfunction remained constant until a late phase of the disease. These data suggest that a GABAergic hyper-responsiveness can compensate for GABA cell loss and protect from occurrence of seizures during latency, whereas impaired extracellular GABA levels can favor the occurrence of spontaneous recurrent seizures and the maintenance of an epileptic state.
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Experimental neurology · Jul 2014
Roles of the periaqueductal gray in descending facilitatory and inhibitory controls of intramuscular hypertonic saline induced muscle nociception.
Despite the importance of the periaqueductal gray (PAG) in the modulation of nociception and pain, many aspects of the roles of the different columns of the PAG in descending controls: facilitation and inhibition, are not understood. Employing a tonic muscle pain model established by i.m. injection of 5.8% saline into the gastrocnemius muscle, we now report the results of investigations designed to explore any differences in Fos expression in the different functional columns of the PAG in male Sprague-Dawley rats. In a second series of experiments, effects of the PAG on descending control of spinally-organized nociception were assessed by measuring hind paw withdrawal reflexes to noxious mechanical and heat stimulation before and after electrolytic lesion of specific columns of the PAG. ⋯ By contrast, contralateral lesion of the vl PAG completely blocked the occurrence of ipsilateral heat hypoalgesia (P<0.05), while bilateral mechanical hyperalgesia was unaffected (P>0.05). In conclusion, functions of specific columns of the PAG in the control of spinal nociceptive activities are not homogeneous. It is suggested that, in this muscle pain model, the dl PAG and vl PAG participate in descending facilitation and inhibition of nociception, respectively.