Glutamine Concentration and Immune Response of Spinal Cord-Injured Rats

Abstract

Background/Objectives: Glutamine plays a key role in immune response. Spinal cord injury (SCI) leads to severe loss of muscle mass and to a high incidence of infections. This study investigated the acute effect of SCI (2 and 5 days) on the plasma glutamine and skeletal muscle concentrations and immune responses in rats. Methods: A total of 29 adult male Wistar rats were divided as follows: control (C; n ¼ 5), sham-operated (S2; n ¼ 5) and spinal cord-transected (T2; n ¼ 7). They were killed on day 2 after surgery/transection (acute phase). Another set was sham-operated (S5; n ¼ 5), spinal cord-transected (T5; n ¼ 7), and killed at day 5 after surgery/transection (secondary phase). Blood was collected; the white portion of the epitrochlearis and gastrocnemius muscles and the red portion of soleus muscles were dissected to measure the glutamine concentration. Gut-associated lymphocytes and peritoneal macrophages were obtained for immune parameters measurements. Results: Glutamine concentration in the plasma, gastrocnemius, and soleus muscles in rats with SCI were significantly reduced but not in the epitrochlearis muscle in the acute (2 days) and secondary (5 days) phases. Phagocytic response was reduced in the acute phase but increased in the secondary phase in rats with SCI. Superoxide production, on the other hand, was significantly increased at days 2 and 5 after SCI, and CD8 þ lymphocytes subset decreased significantly on days 2 and 5. Conclusions: Our results showed reduction in plasma glutamine and skeletal muscle concentrations after spinal cord transection. They also suggest that SCI and glutamine reduction contribute to an alteration in immune competence.

P2Y2 receptor expression is altered in rats after spinal cord injury

“…Spinal cord injury (SCI) leads to a complex series of cellular and molecular events including axotomy, demyelination of surviving axons, nucleotides release, free‐radical production, and release of excitatory amino acids (Franke et al, 2006; Tanhoffer et al, 2007). These events are followed by neural tissue loss due to necrosis, apoptosis, macrophage infiltration, and inflammation (Dijkstra et al, 2001; Hulsebosch, 2002; Iannotti et al, 2006; Popovich et al, 2003).…”

Function of microglia and macrophages in secondary damage after spinal cord injury

“…As summarized from some previous SCI research (Dumont et al, 2001;Ramer et al, 2005;Liu et al, 2006;Tanhoffer et al, 2007;Fehlings and Nguyen, 2010;Varnum and Ikezu, 2012;Zhang et al, 2012), secondary damage/injury after SCI has the following aspects: (1) timing: secondary damage mechanisms initiate within minutes after injury and last for weeks or months; (2) location: secondary damage is not only restricted to the area of the vertebral fracture, but also extends to adjacent segments and even influences the whole body; (3) mechanisms of damage: secondary injury following spinal cord trauma is multifactorial (McCormick, 1998;Ramer et al, 2005) (Table 1); (4) morphology: secondary damage after SCI is characterized by hematoma, edema, glial/axon scarring, and central cavitation; (5) cytokine secretion: pro-inflammatory cytokines and chemokines such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-6, IL-23, leukemia inhibitory factors (LIF) and inducible nitric oxide synthase (iNOS); and anti-inflammatory cytokines such as IL-10, IL-4, IL-13, and transforming growth factor β (TGF-β).…”

Mitochondrial-Based Therapeutics for the Treatment of Spinal Cord Injury: Mitochondrial Biogenesis as a Potential Pharmacological Target

“…Within the first minutes to hours after injury, a secondary cascade is initiated, which can last for weeks or months and whose damaging effects are comparative to, if not greater than, that of the initial insult (Tanhoffer et al, 2007;Oyinbo, 2011). Consequences of secondary injury include progressive axon demyelination (Totoiu and Keirstead, 2005), neuronal cell death (Beattie et al, 2002;Anwar et al, 2016), microglia activation and inflammation (Qiao et al, 2010(Qiao et al, , 2015, glial scar formation (Shibuya et al, 2009), and mitochondrial dysfunction, all of which contribute to the progressive pathology.…”