Cholinergic sympathetic preganglionic neurons (SPN) coexpress the biosynthetic enzyme for acetylcholine, choline acetyl-transferase (ChAT), and neuropeptides such as enkephalin (ENK) in their cell bodies. However, it is not clear whether they also coexpress ChAT and neuropeptides in axon fibers and boutons. To explore coexpression of ChAT and neuropeptides in somata and axon processes of SPN, we investigated, using immunohistochemistry, retrograde labeling, confocal analysis, and tridimensional reconstruction, whether ChAT and the peptides neurotensin, methionine-ENK, somatostatin, calcitonin gene-related peptide, and vasoactive intestinal peptide colocalize in somata, axons fibers, and boutons of cat SPN. Practically, complete colocalization for these peptides and ChAT was observed in SPN somata. Conversely, in most instances we observed independent localization of immunoreactivity (IR) for ChAT and the peptides in axon fibers and boutons. The minor colocalization between ChAT- and peptide-IR in preganglionic fibers could correspond to a sequential axonal transport of ChAT and peptides, since we observed coexistence of these transmitters after blocking axonal transport. Contrary to Dale's principle, our results suggest that SPN can synthesize ChAT and peptides in their cell bodies and route them to distinct axon boutons or terminals in sympathetic ganglia. Presence of axon boutons containing either ChAT or neuropeptides lead us to suggest a new neurochemical pattern of cotransmission in sympathetic ganglia based on the concurrent release of transmitters and cotransmitters from distinct presynaptic boutons, rather than in the corelease of these mediators from the same axon process. The possibility that cellular segregation could be transient and depend on functional requirements is considered.

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The toolkit for repairing damaged neurons in amyotrophic lateral sclerosis (ALS) and spinal cord injury (SCI) is extremely limited. Here, we reviewed the in vitro and in vivo studies and clinical trials on nonneuronal cells in the neurodegenerative processes common to both these conditions. Special focus was directed to microglia and astrocytes, because their activation and proliferation, also known as neuroinflammation, is a key driver of neurodegeneration. Neuroinflammation is a multifaceted process that evolves during the disease course, and can be either beneficial or toxic to neurons. Given the fundamental regulatory functions of glia, pathogenic mechanisms in neuroinflammation represent promising therapeutic targets. We also discussed neuroprotective, immunosuppressive, and stem-cell based approaches applicable to both ALS and SCI.

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Any spinal cord injury carries the potential for persistent disability affecting motor, sensory and autonomic functions. To prevent this outcome, it is highly desirable to block a chain of deleterious reactions developing in the spinal areas immediately around the primary lesion. Thus, early timing of pharmacological neuroprotection should be one major strategy whose impact may be first studied with preclinical models. Using a simple in vitro model of the rat spinal cord it is possible to mimic pathological processes like excitotoxicity that damages neurons because of excessive glutamate receptor activation due to injury, or hypoxic/dysmetabolic insult that preferentially affects glia following vascular dysfunction. While ongoing research is exploring the various components of pathways leading to cell death, current treatment principally relies on the off-label use of riluzole (RLZ) or methylprednisolone sodium succinate (MPSS). The mechanism of action of these drugs is diverse as RLZ targets mainly neurons and MPSS targets glia. Even when applied after a transient excitotoxic stimulus, RLZ can provide effective prevention of secondary excitotoxic damage to premotoneurons, although not to motoneurons that remain very vulnerable. This observation indicates persistent inability to express locomotor activity despite pharmacological treatment conferring some histological protection. MPSS can protect glia from dysmetabolic insult, yet it remains poorly effective to prevent neuronal death. In summary, it appears that these pharmacological agents can produce delayed protection for certain cell types only, and that their combined administration does not provide additional benefit. The search should continue for better, mechanism-based neuroprotective agents.