Nitric oxide (NO) was first recognized as a messenger molecule in the central nervous system (eNS) in 1988 (52), when it was identified as the unstable intercellular factor that had been hypothesized, a year earlier (53), to mediate the increased cyclic GMP (cGMP) levels that occur on activation of glutamate receptors, particularly those of the NMDA (N-methyl-D-aspartate) subtype. The presence of an NO-forming enzyme (NO synthase, or NOS) in the brain was later confirmed (74), and this enzyme was subsequently purified (14) and its cDNA cloned and sequenced (12). The discovery that NO functions as a signaling molecule in the brain opened a new dimension in our concept of neural communication, one overlaying the classical picture of chemical neurotransmission, where information is passed between neuronal elements at discrete loci (synapses), and in one direction, with a diffusive type of signal that disregards the spatial constraints on neu­ rotransmitter activity normally imposed by membranes, transporters, and in­ activating enzymes. In principle, NO could spread out from its site of produc­ tion to influence many different tissue elements (neuronal, glial, and vascular) that are not necessarily in close anatomical juxtaposition. During the past few years, much information on the enzymology and mo­ lecular characteristics of NO synthesis has accrued, as reviewed in other articles in this volume. Furthermore, data from immunocytochemistry, in situ hybridization, and NADPH diaphorase histochemistry have combined to give

Nitric oxide signaling in the central nervous system.

Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins

Functional recovery from peripheral nerve injury and repair depends on a multitude of factors, both intrinsic and extrinsic to neurons. Neuronal survival after axotomy is a prerequisite for regeneration and is facilitated by an array of trophic factors from multiple sources, including neurotrophins, neuropoietic cytokines, insulin-like growth factors (IGFs), and glial-cell-line-derived neurotrophic factors (GDNFs). Axotomized neurons must switch from a transmitting mode to a growth mode and express growth-associated proteins, such as GAP-43, tubulin, and actin, as well as an array of novel neuropeptides and cytokines, all of which have the potential to promote axonal regeneration. Axonal sprouts must reach the distal nerve stump at a time when its growth support is optimal. Schwann cells in the distal stump undergo proliferation and phenotypical changes to prepare the local environment to be favorable for axonal regeneration. Schwann cells play an indispensable role in promoting regeneration by increasing their synthesis of surface cell adhesion molecules (CAMs), such as N-CAM, Ng-CAM/L1, N-cadherin, and L2/HNK-1, by elaborating basement membrane that contains many extracellular matrix proteins, such as laminin, fibronectin, and tenascin, and by producing many neurotrophic factors and their receptors. However, the growth support provided by the distal nerve stump and the capacity of the axotomized neurons to regenerate axons may not be sustained indefinitely. Axonal regenerations may be facilitated by new strategies that enhance the growth potential of neurons and optimize the growth support of the distal nerve stump in combination with prompt nerve repair.

The cellular and molecular basis of peripheral nerve regeneration.

Bright and dark sides of nitric oxide in ischemic brain injury

In a remarkably brief period of time, NO and CO have been recognized as putative neurotransmitters. These two novel messenger molecules have greatly expanded the criteria for candidacy of a chemical for the status of neurotransmitter and our notions about how synaptic transmission takes place. The involvement of NO and CO in several important aspects of neuronal function suggests that agents affecting the synthesis, transactions, and disposition of these gases are bound to have clinical relevance.

https://www.jneurosci.org/content/jneuro/14/9/5147.full.pdf

Gases as biological messengers: nitric oxide and carbon monoxide in the brain

Expression of Nitric-Oxide Synthase (NOS) in Injured CNS Neurons as Shown by NADPH Diaphorase Histochemistry

Neuronal nitric oxide synthase is induced in spinal neurons by traumatic injury.

Potential Roles of Gene Expression Change in Adult Rat Spinal Motoneurons Following Axonal Injury: A Comparison among c-jun, Low-Affinity Nerve Growth Factor Receptor (LNGFR), and Nitric Oxide Synthase (NOS)

Implantation of PNS Graft Inhibits the Induction of Neuronal Nitric Oxide Synthase and Enhances the Survival of Spinal Motoneurons Following Root Avulsion

Wutian Wu

Papers

Expression of Nitric-Oxide Synthase (NOS) in Injured CNS Neurons as Shown by NADPH Diaphorase Histochemistry

Neuronal nitric oxide synthase is induced in spinal neurons by traumatic injury.

Potential Roles of Gene Expression Change in Adult Rat Spinal Motoneurons Following Axonal Injury: A Comparison among c-jun, Low-Affinity Nerve Growth Factor Receptor (LNGFR), and Nitric Oxide Synthase (NOS)

Implantation of PNS Graft Inhibits the Induction of Neuronal Nitric Oxide Synthase and Enhances the Survival of Spinal Motoneurons Following Root Avulsion

Expression of c-jun and neuronal nitric oxide synthase in rat spinal motoneurons following axonal injury