epidermal-growth-factor and Hemiplegia

Among proposed mechanisms to explain digital clubbing, the release of cytokines, specifically vascular endothelial growth factor and platelet-derived growth factor, from aggregated platelets and megakaryocytes has emerged as the most likely explanation. This review describes these and other contributory processes.

Topics: Bradykinin; Cytokines; Epidermal Growth Factor; Ferritins; Hemiplegia; Hepatocyte Growth Factor; Human Growth Hormone; Humans; Hypoxia; Intercellular Signaling Peptides and Proteins; Interleukin-6; Osteoarthropathy, Primary Hypertrophic; Osteoarthropathy, Secondary Hypertrophic; Platelet-Derived Growth Factor; Prostaglandins; Serotonin; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; von Willebrand Factor

While intraventricular administration of epidermal growth factor (EGF) expands the proliferation of neural stem/progenitor cells in the subventricular zone (SVZ), overexpression of brain-derived neurotrophic factor (BDNF) is particularly effective in enhancing striatal neurogenesis. We assessed the induction of striatal neurogenesis and consequent functional recovery after chronic infusion of BDNF and EGF in an adult animal model of neonatal hypoxic-ischemic (HI) brain injury. Permanent brain damage was induced in CD-1 (ICR) mice (P7) by applying the ligation of unilateral carotid artery and hypoxic condition. At 6 weeks of age, the mice were randomly assigned to groups receiving a continuous 2-week infusion of one of the following treatments into the ventricle: BDNF, EGF, BDNF/EGF, or phosphate buffered saline (PBS). Two weeks after treatment, immunohistochemical analysis revealed an increase in the number of BrdU(+) cells in the SVZ and striata of BDNF/EGF-treated mice. The number of new neurons co-stained with BrdU and betaIII-tubulin was also significantly increased in the neostriata of BDNF/EGF-treated mice, compared with PBS group. In addition, the newly generated cells were expressed as migrating neuroblasts labeled with PSA-NCAM or doublecortin in the SVZ and the ventricular side of neostriata. The new striatal neurons were also differentiated as mature neurons co-labeled with BrdU(+)/NeuN(+). When evaluated post-surgical 8 weeks, BDNF/EGF-treated mice exhibited significantly longer rotarod latencies at constant speed (48 rpm) and under accelerating condition (4-80 rpm), relative to PBS and untreated controls. In the forelimb-use asymmetry test, BDNF/EGF-treated mice showed significant improvement in the use of the contralateral forelimb. In contrast, this BDNF/EGF-associated functional recovery was abolished in mice receiving a co-infusion of 2% cytosine-b-d-arabinofuranoside (Ara-C), a mitotic inhibitor. Induction of striatal neurogenesis by the intraventricular administration of BDNF and EGF promoted functional recovery in an adult animal model of neonatal HI brain injury. The effect of Ara-C to completely block functional recovery indicates that the effect may be the result of newly generated neurons. Therefore, this treatment may offer a promising strategy for the restoration of motor function for adults with cerebral palsy (CP).

Topics: Animals; Ataxia; Brain Damage, Chronic; Brain-Derived Neurotrophic Factor; Carotid Arteries; Cerebral Palsy; Corpus Striatum; Cytarabine; Disease Models, Animal; Drug Evaluation, Preclinical; Epidermal Growth Factor; Forelimb; Hemiplegia; Hypoxia; Hypoxia-Ischemia, Brain; Infusions, Intraventricular; Ligation; Mice; Mice, Inbred ICR; Neurogenesis; Random Allocation; Recovery of Function

We assessed the effect of a 35-day delayed intracerebroventricular (ICV) infusion of epidermal growth factor (EGF) on the survival and function of the substantia nigra (SN) dopaminergic neurons after a unilateral mechanical transection of rat nigrostriatal pathway. EGF infusion for 28 days resulted in a twofold increase in the number of surviving tyrosine-hydroxylase (TH)-positive SN neurons and a significant increase in ipsilateral striatal TH-positive fiber staining compared to controls at 200 days following the injury. In addition, there was a persistent enhancement of behavioral recovery, as indicated by a reduction in amphetamine-induced rotations. We conclude that EGF exerts a neurotrophic effect on the dopaminergic neurons in this experimental model of parkinsonism.

Topics: Animals; Corpus Striatum; Epidermal Growth Factor; ErbB Receptors; Hemiplegia; Male; Medial Forebrain Bundle; Motor Activity; Nerve Regeneration; Parkinson Disease, Secondary; Rats; Rats, Inbred Strains; Receptors, Dopamine; Stereotyped Behavior; Substantia Nigra; Tyrosine 3-Monooxygenase