Basic fibroblast growth factor alleviates brain injury following global ischemia reperfusion in rabbits

Abstract

Abstract:The aim of this study was to explore the protective effect of basic fibroblast growth factor (bFGF) on brain injury following global ischemia reperfusion and its mechanisms. Brain injury following global ischemia was induced by four vessels occlusion and systemic hypotension. Twenty-four rabbits were randomized into three groups: group A, only dissection of vessels; group B, intravenous infusion of normal saline after reperfusion for 6 h; group C, 30 µg/kg bFGF injected intravenously at the onset of reperfusion, then infused with 10 µg/(kg⋅h) for 6 h. Serum neuron specific enolase (NSE), S-100B, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-8 (IL-8) were measured before ischemia, 30 min after ischemia, 0.5, 1, 3, 6 h after reperfusion. Brain water content was determined and cerebral histopathological damages were compared. NSE and S-100B were increased 1 h after reperfusion and reached their peaks 6 h after reperfusion, but were much higher in group B than those in group C 3, 6 h after reperfusion. In groups B and C, TNF-α was increased after ischemia and IL-1 and IL-8 were increased significantly 0.5 h after reperfusion, then reached their peaks 6 h, 3 h, 6 h after reperfusion respectively. TNF-α and IL-8 at the time points of 1 h and 3 h and IL-1 at 3 h and 6 h in group C were correspondingly lower than those in group B. These indices in group A were nearly unchanged. There were less severe cerebral histopathological damages in group C compared with group B, but no difference in brain water content. It could be concluded that bFGF alleviates brain injury following global ischemia and reperfusion by down-regulating expression of inflammatory factors and inhibiting their activities.

The Role of bFGF in the Excessive Activation of Astrocytes Is Related to the Inhibition of TLR4/NFκB Signals

“…The therapeutic potential of exogenous bFGF in CNS diseases has been well-recognized for decades [ 34 , 35 ], but the underlying mechanism in astrocyte activation is still under debate. It has been suggested that the observed increase of bFGF after neural injury would further activate astrocytes [ 36 , 37 ].…”

“…In a latest study, IL-6, IL-1β, and TNF-α were inhibited by ulinastatin in LPS-stimulated astrocytes [ 33 ]. bFGF was found to down-regulate the expression of TNF-α and IL-1 following ischemia and reperfusion, which contributed to alleviating brain injury [ 35 ]. In the urinary tissue of the bladder, bFGF also reduced the production of TNF-α and IL-1β at early phases of radiation-induced injury [ 49 ].…”

Neuron specific enolase: a promising therapeutic target in acute spinal cord injury

“…NSE consists of two γ subunits and converts 2-phosphoglycerate into phosphoenolpyruvate [2]. NSE is thought to be a marker of ischemic brain damage, and it has been shown to be elevated in stroke [36], traumatic brain injury (TBI) [37, 38], ischemia-reperfusion injury (IRI) [39], and SCI [40, 41]. …”

Biological functions of the low and high molecular weight protein isoforms of fibroblast growth factor‐2 in cardiovascular development and disease

“…There is evidence that the LMW isoform of FGF2 participates in cardiac (Unger et al,1994; Padua et al,1995,1998; Hasdai et al,1997; Horrigan et al,1999; Cuevas et al,2000; Sheikh et al,2001; Liao et al,2007b), renal (Villanueva et al,2006), intestinal (Fu et al,2003), and cerebral (Jiang et al,1996; Cheung et al,2000; Zhang et al,2005) I‐R injury. These actions of the FGF2 LMW isoform may involve, but do not require, angiogenic activity.…”

“…Exogenous treatment with LMW isoform increases capillary density and blood flow in the ischemic myocardium by means of growth of new collateral vessels (Unger et al,1994) and induces nephrogenic proteins after acute ischemic renal failure (Villanueva et al,2006). In the brain, exogenous administration of FGF2 LMW isoform alleviates brain injury following global ischemia and reperfusion by down‐regulating the expression of inflammatory factors and inhibiting their activities (Zhang et al,2005). In the isolated adult rat or mouse heart model, recombinant rat FGF2 LMW isoform given by retrograde perfusion protects the heart from subsequent I‐R–induced contractile dysfunction and myocardial cell damage and preserves cardiac energy metabolism (Padua et al,1995).…”