Pattern of chondroitin sulfate proteoglycan expression after ablation of the sensorimotor cortex of the neonatal and adult rat brain

The central nervous system has a limited capacity for self-repair after damage. However, the neonatal brain has agreater capacity for recovery than the adult brain. These differences in the regenerative capability depend on local environmental factors and the maturational stage of growing axons. Among molecules which have both growth-promoting and growth-inhibiting activities is the heterogeneous class of chondroitin sulfate proteoglycans (CSPGs). In this paper, we investigated the chondroitin-4 and chondroitin-6 sulfate proteoglycan expression profile after left sensorimotor cortex ablation of the neonatal and adult rat brain. Immunohistochemical analysis revealed that compared to the normal uninjured cortex, lesion provoked up regulation of CSPGs showing a different pattern of expression in the neonatal vs. the adult brain. Punctuate and membrane-bound labeling was predominate after neonatal lesion, where as heavy deposition of staining in the extracellular matrix was observed after adult lesion. Heavy deposition of CSPG immunoreactivity around the lesionsite in adult rats, in contrast to a less CSPG-rich environment in neonatal rats, indicated that enhancement of the recovery process after neonatal injury is due to amore permissive environment

Brain cortical injury induces changes in peripheral lymphocyte ectonucleotidase activities

Injury and other pathological conditions induce a massive release of ATP and ADP that initiate an immune response. Extracellular nucleotides are degraded by ectonucleotidases: enzymes from E-NTPDase and E-NPP families sequentially hydrolyze ATP and ADP to AMP, which is further hydrolyzed by ecto-5'-nucleotidase to adenosine that exerts suppressive effects on immune cells. We investigated the ectonucleotidase activities of peripheral lymphocytes at different post-injury times after an unilateral brain injury in the rat. Significant and dynamic changes in the lymphocytic ectonucleotidase activities were obtained. ATP- and ADP-hydrolysis changes, together with their calculated ratios, indicate the major contribution of E-NTPDase 1 and its comparable upregulation between sham operation and injury. AMP hydrolysis changes were more brain-injury specific, with a longer-lasting lymphocytic response induced by cortical stab injury (CSI). In summary, CSI and sham operation induce the upregulation of the whole enzyme chain for adenine nucleotide hydrolysis in lymphocytes, suggesting an important roles of ectonucleotidases in the course of recovery after brain injury.Projekat ministarstva br. III4101

Pattern of chondroitin sulfate proteoglycan expression after ablation of the sensorimotor cortex of the neonatal and adult rat brain

The central nervous system has a limited capacity for self-repair after damage. However, the neonatal brain has agreater capacity for recovery than the adult brain. These differences in the regenerative capability depend on local environmental factors and the maturational stage of growing axons. Among molecules which have both growth-promoting and growth-inhibiting activities is the heterogeneous class of chondroitin sulfate proteoglycans (CSPGs). In this paper, we investigated the chondroitin-4 and chondroitin-6 sulfate proteoglycan expression profile after left sensorimotor cortex ablation of the neonatal and adult rat brain. Immunohistochemical analysis revealed that compared to the normal uninjured cortex, lesion provoked up regulation of CSPGs showing a different pattern of expression in the neonatal vs. the adult brain. Punctuate and membrane-bound labeling was predominate after neonatal lesion, where as heavy deposition of staining in the extracellular matrix was observed after adult lesion. Heavy deposition of CSPG immunoreactivity around the lesionsite in adult rats, in contrast to a less CSPG-rich environment in neonatal rats, indicated that enhancement of the recovery process after neonatal injury is due to amore permissive environment.Centralni nervni sistem ima ograničen kapacitet za oporavak nakon povrede. Međutim, neonatalni mozak pokazuje veću sposobnost oporavka u odnosu na odrasle. Ove razlike zavise od lokalnih sredinskih faktora i stepena zrelosti aksona tokom izrastanja. U grupu molekula koji mogu da stimulišu ili inhibiraju rast aksona spada i heterogena klasa molekula označena kao hondroitin sulfatni proteoglikani (CSPG). U ovom radu ispitivanje profil ekspresije hondroitin-4 i hondroitin-6 sulfatnih proteoglikana nakonlezije leve senzomotorne kore neonatalnog i adultnog mozga pacova. Imunohistohemijska analiza pokazuje da u odnosu na normalni,nepovređeni korteks, lezija dovodi do povećanja ekspresije CSPG koji ima različiti obrazac promena u neonatalnom u odnosu na adultni mozak. Nakonlezije kod mladih, predominiraju tačkasta i membranski-vezana forma, dok kod odraslih lezija dovodi do nagomilavanja CSPG u ekstra ćelijskom matriksu. Prohodnija sredina u mozgu neonatalnih pacova koja je siromašnija CSPG, preduslov je boljeg procesa oporavka u odnosu na adulte, kod kojih se nakon povrede CSPG nagomilavaju oko mesta lezije.Projekat ministarstva br. 143005

Therapeutic effect of nucleoside analogs on experimental autoimmune encephalomyelitis in dark agouti rats

Experimental autoimmune encephalomyelitis (EAE) is a commonly used animal model of the human neurological disorder multiple sclerosis. The purpose of the present study was to investigate the effect of combined treatment with two nucleoside analogs, ribavirin and tiazofurin, on development of EAE actively induced in highly susceptible dark agouti rats. The obtained results showed that ribavirin and tiazofurin applied either separately or in combination from the onset of the firstsymptoms of EAE after its induction (therapeutic treatment) significantly suppressed EAE’s clinical symptoms. However, the most pronounced effect was gained with combined treatment, probably as a result of synergistic/additive action

Pattern of chondroitin sulfate proteoglycan expression after ablation of the sensorimotor cortex of the neonatal and adult rat brain

The central nervous system has a limited capacity for self-repair after damage. However, the neonatal brain has agreater capacity for recovery than the adult brain. These differences in the regenerative capability depend on local environmental factors and the maturational stage of growing axons. Among molecules which have both growth-promoting and growth-inhibiting activities is the heterogeneous class of chondroitin sulfate proteoglycans (CSPGs). In this paper, we investigated the chondroitin-4 and chondroitin-6 sulfate proteoglycan expression profile after left sensorimotor cortex ablation of the neonatal and adult rat brain. Immunohistochemical analysis revealed that compared to the normal uninjured cortex, lesion provoked up regulation of CSPGs showing a different pattern of expression in the neonatal vs. the adult brain. Punctuate and membrane-bound labeling was predominate after neonatal lesion, where as heavy deposition of staining in the extracellular matrix was observed after adult lesion. Heavy deposition of CSPG immunoreactivity around the lesionsite in adult rats, in contrast to a less CSPG-rich environment in neonatal rats, indicated that enhancement of the recovery process after neonatal injury is due to amore permissive environment.Centralni nervni sistem ima ograničen kapacitet za oporavak nakon povrede. Međutim, neonatalni mozak pokazuje veću sposobnost oporavka u odnosu na odrasle. Ove razlike zavise od lokalnih sredinskih faktora i stepena zrelosti aksona tokom izrastanja. U grupu molekula koji mogu da stimulišu ili inhibiraju rast aksona spada i heterogena klasa molekula označena kao hondroitin sulfatni proteoglikani (CSPG). U ovom radu ispitivanje profil ekspresije hondroitin-4 i hondroitin-6 sulfatnih proteoglikana nakonlezije leve senzomotorne kore neonatalnog i adultnog mozga pacova. Imunohistohemijska analiza pokazuje da u odnosu na normalni,nepovređeni korteks, lezija dovodi do povećanja ekspresije CSPG koji ima različiti obrazac promena u neonatalnom u odnosu na adultni mozak. Nakonlezije kod mladih, predominiraju tačkasta i membranski-vezana forma, dok kod odraslih lezija dovodi do nagomilavanja CSPG u ekstra ćelijskom matriksu. Prohodnija sredina u mozgu neonatalnih pacova koja je siromašnija CSPG, preduslov je boljeg procesa oporavka u odnosu na adulte, kod kojih se nakon povrede CSPG nagomilavaju oko mesta lezije.Projekat ministarstva br. 143005

Brain cortical injury induces changes in peripheral lymphocyte ectonucleotidase activities

Injury and other pathological conditions induce a massive release of ATP and ADP that initiate an immune response. Extracellular nucleotides are degraded by ectonucleotidases: enzymes from E-NTPDase and E-NPP families sequentially hydrolyze ATP and ADP to AMP, which is further hydrolyzed by ecto-5’-nucleotidase to adenosine that exerts suppressive effects on immune cells. We investigated the ectonucleotidase activities of peripheral lymphocytes at different post-injury times after an unilateral brain injury in the rat. Significant and dynamic changes in the lymphocytic ectonucleotidase activities were obtained. ATP- and ADP-hydrolysis changes, together with their calculated ratios, indicate the major contribution of E-NTPDase 1 and its comparable upregulation between sham operation and injury. AMP hydrolysis changes were more brain-injury specific, with a longer-lasting lymphocytic response induced by cortical stab injury (CSI). In summary, CSI and sham operation induce the upregulation of the whole enzyme chain for adenine nucleotide hydrolysis in lymphocytes, suggesting an important roles of ectonucleotidases in the course of recovery after brain injury. [Projekat Ministarstva nauke Republike Srbije, br. III41014

Regional changes in ectonucleotidase activity after cortical stab injury in rat

During a variety of insults to the brain adenine nucleotides are released in large quantities from damaged cells, triggering local cellular and biochemical responses to injury. Different models of brain injury reveal that the local increase in adenine nucleotides levels is followed by a compensatory up-regulation of ectonucleotidase enzymes that catalyze sequential hydrolysis of ATP to ADP, AMP and adenosine. However, recent studies imply that changes in adenine nucleotides release may also occur in the areas distant from the site of direct damage. Therefore, in the present study we have used the model of cortical stab injury to analyze extracellular ATP, ADP and AMP hydrolysis in the membrane preparations obtained from the brain regions that were not subjected to direct tissue damage. The brain regions analyzed were contralateral cortex, hippocampus, caudate nucleus, thalamus and hypothalamus. It was evidenced that cortical stab injury induced early widespread decrease in AMP hydrolysis in all brain areas tested, except in the hypothalamus, without changes in ATP hydrolysis. These findings imply that brain injury affects global extracellular adenine nucleotide and nucleoside levels, consequently affecting neuronal function in the regions distant to the primary damage.Serbian Ministry of Science and Technological Development [143005

Regional changes in ectonucleotidase activity after cortical stab injury in rat

During a variety of insults to the brain adenine nucleotides are released in large quantities from damaged cells, triggering local cellular and biochemical responses to injury. Different models of brain injury reveal that the local increase in adenine nucleotides levels is followed by a compensatory up-regulation of ectonucleotidase enzymes that catalyze sequential hydrolysis of ATP to ADP, AMP and adenosine. However, recent studies imply that changes in adenine nucleotides release may also occur in the areas distant from the site of direct damage. Therefore, in the present study we have used the model of cortical stab injury to analyze extracellular ATP, ADP and AMP hydrolysis in the membrane preparations obtained from the brain regions that were not subjected to direct tissue damage. The brain regions analyzed were contralateral cortex, hippocampus, caudate nucleus, thalamus and hypothalamus. It was evidenced that cortical stab injury induced early widespread decrease in AMP hydrolysis in all brain areas tested, except in the hypothalamus, without changes in ATP hydrolysis. These findings imply that brain injury affects global extracellular adenine nucleotide and nucleoside levels, consequently affecting neuronal function in the regions distant to the primary damage.Serbian Ministry of Science and Technological Development [143005

Arch. Biol. Sci��� � Be������de� � 60 (4�� � 581-591� � 2008 DOI:10��2298/ABS0804581D PATTERN OF CHONDROITIN SULFATE PROTEOGLYCAN EXPRESSION AFTER ABLATION OF THE SENSORIMOTOR CORTEX OF THE NEONATAL AND ADULT RAT BRAIN

Abstract — The cen�t��� � n�ervous s��stem has a ��imited capacit� � for se�����epair after d�����e� � Howeve�� � the n�eon��t�� � brain� has a ���eater capacit� � for recove�� � t��n � the adu��t brain�� � These differen��es in � the re��en�erative capabi��it� � depen�d on � ��o���� en��iron��en�t�� � factors �n�d the maturation��� � st���e of ���owin�� � axon�s� � Amon�� � mo��ecu��es which have both ���owth-pro� motin�� � �n�d ���owth-in��ibitin�� � activities is the hetero��en�eous ����ss of chon�droitin � su����te proteo��������n�s (CSPGs�� � In � this pape�� � we in��esti���ted the chon�droitin��4 �n�d chon�droitin�� � su����te proteo��������n � expression � profi��e after ��eft sen�sorimotor cortex �����tion � of the n�eon��t�� � �n�d adu��t rat brain�� � Immun�ohistochemi��� � �n������sis reve���ed that compared to the n�o����� un�in�jured cortex� � ��esion � provoked upre��u���tion � of CSPGs showin�� � a differen�t patte�n � of expression � in � the n�eon��t�� � vs�� the adu��t brain�� � Pun��tuate �n�d me����n�e-boun�d ����e��in�� � was predomin��te after n�eon��t�� � ��esion�� � whereas he��� � deposi� tion � of stain�in�� � in � the extrace����u��� � matrix was observed after adu��t ��esion�� � He��� � deposition � of CSPG immun�oreactivit�� aroun�d the ��esion � site in � adu��t rats� � in � con�trast to a ��ess CSPG-rich en��iron��en�t in � n�eon��t�� � rats� � in�dicated that en���n��e� men�t of the recove�� � process after n�eon��t�� � in�ju�� � is due to a more permissive en��iron��en�t�� Key words: Brain � in�ju���� � chon�droitin � su����te proteo��������n�s� � n�eon��t�� � �n�d adu��t rat brain�� � deve��opmen�t Udc 5����4:�����831:577��21

Early temporal changes in ecto-nucleotidase activity after cortical stab injury in rat

During a variety of insults to the brain adenine nucleotides are released in large quantities from damaged cells, triggering multiple cellular responses to injury. Here, we evaluated changes in extracellular ATP, ADP and AMP hydrolysis at different times (0-24 hours) after unilateral cortical stab injury (CSI) in adult rats. Results demonstrated that 24 hours following CSI, ATP and ADP hydrolyzing activities were not significantly altered in injured cortex. Based on calculated V (ATP)/V (ADP) ratio it was concluded that ATP/ADP hydrolysis was primarily catalyzed by NTPDase1 enzyme form. In contrast, AMP hydrolysis, catalyzed by 5'-nucleotidase, was significantly reduced at least 4 hours following CSI. Kinetic analysis and Lineweaver-Burk transformation of the enzyme velocities obtained over the range of AMP concentrations (0.05-1.50 mM) revealed that inhibition of 5'-nucleotidase activity after CSI was of the uncompetitive type. Taken together our data suggest that injured tissue has reduced potential for extracellular metabolism of adenine nucleotides in early stages after CSI.nul