Protective effect of a new hypothalamic peptide against cobra venom and trauma-induced neuronal injury.
A study of separate and combined actions of cobra venom (CV) and a new hypothalamic proline-rich polypeptide (PRP) isolated from magnocellular cells (NPV and NSO) on intoxication- and trauma-induced neuronal injury (during 3-4 weeks after hemisection with and without PRP treatment) was carried out. The registration of background and evoked impulse activity flow, changes in spinal cord (SC) inter- and motoneurons, responding to flexor, extensor, and mixed nerve stimulation in both acute and chronic experimental neurodegeneration was performed. The facilitating effect of PRP on the abovementioned neurons was revealed. High doses of CV that evoked the neurodegenerative changes demonstrated an inhibitory effect. In this case PRP treatment both before and after intoxication restored electrical neuronal activity to baseline level and higher. These results are evidence of protective action of PRP. The low doses of CV induced a facilitating effect. The combination of CV and PRP displayed an additive facilitating effect; in a number of cases the repeated administration of CV led to decrease of significant PRP effect till baseline level (for example, the inhibition after primary response prior to secondary late discharge). Greater liability of the secondary early and late long-time discharges of poststimulus responses, differently expressed in various neuron types of SC to chemical influences is of interest. PRP-induced inhibition of the paroxysmal activity related with CV action is also very interesting. Morpho-functional experiments with SC injury demonstrated the abolition of difference in the background and evoked SC neuronal activity below the section and on intact symmetric side after daily PRP administration for 3 weeks. PRP hindered the scar formation and activated neuroglia proliferation; it promoted white matter element growth, hampered the degeneration of cellular elements, and protected against tissue stress. Our results favor the combined use of PRP and CV in clinical practice for the treatment of neurodegeneration of toxic and traumatic origin, as well as specific neurodegenerative diseases such as Alzheimer's.
Galoyan
A A
AA
Bunatian Institute of Biochemistry, NAS RA, Yerevan, The Republic of Armenia. galoyan@sci.am
Sarkissian
J S
JS
Kipriyan
T K
TK
Sarkissian
E J
EJ
Chavushyan
E A
EA
Sulkhanyan
R M
RM
Meliksetyan
I B
IB
Abrahamyan
S S
SS
Grigorian YKh
Avetisyan
Z A
ZA
Otieva
N A
NA
D000818:Animals; D004546:Elapid Venoms / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D055232:Proline-Rich Protein Domains; D051381:Rats; D017208:Rats, Wistar; D014947:Wounds and Injuries / Q000517:prevention & control*
D004546:Elapid Venoms; D010455:Peptides