Vasculitic peripheral neuropathy induced by ischemia-reperfusion in the rat femoral artery involves activation of proinflammatory signaling pathway in the sciatic nerve.

Ischemia-reperfusion (IR) in the rat femoral artery has been proposed as an experimental model of vasculitic peripheral neuropathy (VPN) which presents neuropathic pain and peripheral nerve injury patterns observed clinically. This study investigates the involvement of the proinflammatory signaling pathway underlying the peripheral mechanisms of VPN. Male Sprague-Dawley rats were allocated to receive either a sham operation or IR. IR was induced by occluding the right femoral artery for 4h followed by reperfusion periods from 0 to 72h. The behavioral parameters were assessed at baseline as well as at days 1, 2 and 3 after reperfusion. The time-course analyses of proinflammatory mediators in the sciatic nerves were also performed on rats of the sham group or IR groups with reperfusion periods of 0, 2, 4, 24 and 72h, respectively. The behavioral data confirmed that this VPN model induced hindpaw mechano-allodynia and heat hyperalgesia as well as impaired hindpaw grip strength. The molecular data revealed that IR in the femoral artery activated the expression of nuclear factor-κB (NF-κB) in the sciatic nerve indicating a neuroinflammatory response. Moreover, IR in the femoral artery increased the expression of proinflammatory cytokines TNF-α and IL-1ß in the sciatic nerve. This study elucidated the novel time-course expression profiles of NF-κB and proinflammatory cytokines in VPN induced by IR which may be involved in the development of neuropathic pain. Since NF-κB is a key element during neuroinflammation, strategies targeting the NF-κB signaling pathway may provide therapeutic potential against VPN induced by IR.

Dimethyl Sulfoxide Attenuates Acute Lung Injury Induced by Hemorrhagic Shock/Resuscitation in Rats.

Inflammation following hemorrhagic shock/resuscitation (HS/RES) induces acute lung injury (ALI). Dimethyl sulfoxide (DMSO) possesses anti-inflammatory and antioxidative capacities. We sought to clarify whether DMSO could attenuate ALI induced by HS/RES. Male Sprague-Dawley rats were allocated to receive either a sham operation, sham plus DMSO, HS/RES, or HS/RES plus DMSO, and these were denoted as the Sham, Sham + DMSO, HS/RES, or HS/RES + DMSO group, respectively (n = 12 in each group). HS/RES was achieved by drawing blood to lower mean arterial pressure (40-45 mmHg for 60 min) followed by reinfusion with shed blood/saline mixtures. All rats received an intravenous injection of normal saline or DMSO immediately before resuscitation or at matching points relative to the sham groups. Arterial blood gas and histological assays (including histopathology, neutrophil infiltration, and lung water content) confirmed that HS/RES induced ALI. Significant increases in pulmonary expression of tumor necrosis factor-α (TNF-α), malondialdehyde, nuclear factor-kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2) confirmed that HS/RES induced pulmonary inflammation and oxidative stress. DMSO significantly attenuated the pulmonary inflammation and ALI induced by HS/RES. The mechanisms for this may involve reducing inflammation and oxidative stress through inhibition of pulmonary NF-κB, TNF-α, iNOS, and COX-2 expression.