Increased 5-hydroxytryptamine immunoreactivity in traumatized spinal cord

Abstract

The possibility that serotonin (5-hydroxytryptamine, 5-HT) is involved in the early tissue reactions occurring in spinal cord trauma was examined in a rat model using an immunocytochemical technique. The injury was made in the form of a 5-mm long and 2.5-mm wide lesion of the right dorsal horn at the level of T10-11. Injured rats, pretreated with the 5-HT synthesis blocking agent, p-chlorophenyl alanine (p-CPA) were compared with untreated injured controls and the animals were allowed to survive for 5 h. The distribution of 5-HT was examined in proximal and distal cross- sections of the cord, located 2 and 5 mm away from the injury. Normal rats showed immunoreactive material in nerve cell processes and in a few nerve cell bodies of the ventral horns. The trauma to the spinal cord caused a marked increase in 5-HT immunoreactivity in the segments located 2 mm proximal and distal to the injury, particularly in the ipsilateral ventral horn. The segment located 5 mm distal to the lesion showed a similar increase in immunoreactivity but it was apparently less pronounced in the corresponding proximal segment. Treatment with p-CPA markedly reduced the trauma-induced increase in 5-HT immunoreactivity in all the segments. These immunohistochemical findings were in line with the changes in the contents of 5-HT measured biochemically in corresponding spinal cord segments. At the onset of the trauma to the spinal cord 5-HT is thus present in the tissue, mainly in the form of 5-HT-containing nerve cell processes.(ABSTRACT TRUNCATED AT 250 WORDS)

The Unusual Response of Serotonergic Neurons after CNS Injury: Lack of Axonal Dieback and Enhanced Sprouting within the Inhibitory Environment of the Glial Scar

“…Serotonergic fibers tend to naturally sprout after injury (Sharma et al, 1990; Zhou et al, 1995; Inman and Steward, 2003; Camand et al, 2004), but the mechanism by which they sprout has not been investigated. Here, we used in vitro modeling of an in vivo lesion to show that β1 integrin binding to laminin is critical for serotonergic neurite outgrowth.…”

“…These neurons have the added tendency to sprout after injury, whether caused by direct chemical lesion (Zhou et al, 1995) or spinal cord trauma (Sharma et al, 1990; Inman and Steward, 2003; Camand et al, 2004). When transplanted into the injured adult spinal cord, serotonergic neurons can elongate and incorporate remarkably well into the CNS parenchyma (Privat et al, 1986; Foster et al, 1989; Yakovleff et al, 1995; Feraboli-Lohnherr et al, 1997; Ribotta et al, 2000), where they can bring about a measure of functional recovery.…”

Drug Delivery to the Spinal Cord Tagged with Nanowire Enhances Neuroprotective Efficacy and Functional Recovery following Trauma to the Rat Spinal Cord

“…Thus, various methods are used to enhance drug delivery to the central nervous system (CNS) in normal or in pathological conditions to achieve therapeutic success 11 . Our laboratory was the first to use topical application of several drugs and antibodies over the traumatized spinal cord to achieve enhanced neuroprotection 14–19 . Results from our investigations show that topical application of several drugs, antibodies, or compounds resulted in enhanced neuroprotection compared to their delivery through systemic circulation 1,2,16–18,20,21 .…”

Pathophysiology of Blood-Spinal Cord Barrier in Traumatic Injury and Repair

“…Spinal cord ischemia and spread of edema fluid determines the longitudinal and transverse expansion of the pathological changes within the uninjured cord. These pathological changes at a later stage are somehow influenced by activation of endogenous repair mechanisms [59,62,63,74,75,[105][106][107][108][109][110][111][112].…”

“…However, further studies using pharmacological approaches are needed to clarify this point. In our SCI model, we measured local blood flow in several spinal cord segments using radiolabelled microsphere [70,110]. The most pronounced reduction in the spinal cord blood flow (SCBF) is seen within 15 min in the traumatised region that is progressive in nature up to 8 h (Fig.…”