Behavioral Improvement and Regulation of Molecules Related to Neuroplasticity in Ischemic Rat Spinal Cord Treated with PEDF

Abstract

Pigment epithelium derived factor (PEDF) exerts trophic actions to motoneurons and modulates nonneuronal restorative events, but its effects on neuroplasticity responses after spinal cord (SC) injury are unknown. Rats received a low thoracic SC photothrombotic ischemia and local injection of PEDF and were evaluated behaviorally six weeks later. PEDF actions were detailed in SC ventral horn (motor) in the levels of the lumbar central pattern generator (CPG), far from the injury site. Molecules related to neuroplasticity (MAP-2), those that are able to modulate such event, for instance, neurotrophic factors (NT-3, GDNF, BDNF, and FGF-2), chondroitin sulfate proteoglycans (CSPG), and those associated with angiogenesis and antiapoptosis (laminin and Bcl-2) and Eph (receptor)/ephrin system were evaluated at cellular or molecular levels. PEDF injection improved motor behavioral performance and increased MAP-2 levels and dendritic processes in the region of lumbar CPG. Treatment also elevated GDNF and decreased NT-3, laminin, and CSPG. Injury elevated EphA4 and ephrin-B1 levels, and PEDF treatment increased ephrin A2 and ephrins B1, B2, and B3. Eph receptors and ephrins were found in specific populations of neurons and astrocytes. PEDF treatment to SC injury triggered neuroplasticity in lumbar CPG and regulation of neurotrophic factors, extracellular matrix molecules, and ephrins.

PEDF Reduces the Severity of Herpetic Simplex Keratitis in Mice

“…18,[35][36][37] In corneal HSV-1 infection, a recent report showed that PEDF plus DHA treatment promoted inflammation resolution and induced nerve regeneration in rabbit model. 22 In the present study, we first examined the change of corneal PEDF expression and explored the direct roles of exogenous PEDF treatment in mouse HSK model, focusing on the prevention of corneal neovascularization, nerve degradation, sensation impairment, acute inflammation, and viral replication.…”

Physiopathology of Spinal Cord Injury

“…As mentioned earlier, the ischemic process is another mechanism through which secondary damage occurs. One of the achievements of modern vascular neurology is the description of the vascular, cellular, and biochemical changes that constitute this process [12]. The primary spinal cord injury generates a spinal cord shock, with the consequent neurogenic shock.…”

“…Ischemic damage is constituted by the dynamic interaction between neurons, astrocytes, fibroblasts, smooth muscle, and endothelial cells that interact with the formed elements of the blood leading to cell death [12]. The main biochemical events that occur in this ischemic process are inhibition of protein synthesis, depression of intracellular energy reserves, depolarization of the cell membrane, release of intracellular K + followed by the release of neurotransmitters, Ca 2+ influx to the cell, and cellular metabolic commitment, which leads to lipidic peroxidation that ultimately results in neuronal nuclear destruction and death.…”

In vivo and in vitro models of traumatic injuries of the spinal cord

“…In general, various options of the simulated injury in vivo can be grouped by similar mechanisms of SC lesion and certain behavioral tests are better for them. For example, to assess functional activity of animals at modeling spinal cord injury by ischemia, tests that assess the strength of limbs are more suitable: inclined plane test, rump height index [35,37]. At a model of compression and concussion, tests with different sensitivity that determine restoration of the spinal cord motor functions are better suited to assess the functional activity of the animals after the injuries.…”

“…Another advantage of this model is the ability to decide on the aperture of illumination for different size of lesion as opposed to great vessels clamping when distal part of the SC below the occlusion is completely affected. Moreover, this injury does not result in high mortality of animals and it may be possible to monitor the processes of inflammation and regeneration in spinal cord [37,38]. The disadvantages of this method is that the model does not reflect the fullness of tissue damage characteristic of real conditions, in particular, there is no clear anatomic ischemic shadow and penumbra.…”