Biomedical subjects

Caroline Gahm

Publications and source records attributed to Caroline Gahm.

3 recordsLinked to original sources

PubMed2006

Neuroprotection by selective inhibition of inducible nitric oxide synthase after experimental brain contusion.

The inflammatory response is thought to be important for secondary damage following traumatic brain injury (TBI). The inducible nitric oxide synthase (iNOS) isoform is a mediator in inflammatory reactions and may catalyze substantial synthesis of NO in the injured brain. This study was undertaken to analyze neuronal degeneration and survival, cellular apoptosis and formation of nitrotyrosine following treatment with the iNOS-inhibitor L-N-iminoethyl-lysine (L-NIL) in a model of brain contusion. A brain contusion was produced using a weight-drop device in 30 rats. The animals received treatment with L-NIL or NaCl at 15 min and 12 h after the injury and were sacrificed at 24 h or 6 days after trauma. iNOS activity was measured at 24 h post-trauma by the conversion of L-[U- ( 14 )C]arginine to L-[U-( 14 )C]citrulline and immunohistochemistry for iNOS. Peroxynitrite formation was indirectly assessed by nitrotyrosine (NT) immunohistochemistry. Neuronal degeneration and survival were assessed by Fluoro-Jade (FJ) and NeuN stainings, and cellular death by TUNEL staining. iNOS activity but not iNOS immunoreactivity was significantly reduced in animals that received L-NIL. Neuronal degeneration (FJ) and NT immunoreactivity were significantly reduced at 24 h. Neuronal survival was unchanged at 24 h but increased at 6 days in L-NIL-treated animals. Cellular apoptosis of ED-1 and NeuN positive cells was significantly reduced following L-NIL treatment at 6 days after trauma. We demonstrated neuroprotection by selective inhibition of iNOS after trauma. L-NIL appeared to protect the injured brain by limiting peroxynitrite formation. Our findings support a putative harmful role of iNOS induction early after TBI.

Animals↗

PubMed2005

Reduced neuronal injury after treatment with NG-nitro-L-arginine methyl ester (L-NAME) or 2-sulfo-phenyl-N-tert-butyl nitrone (S-PBN) following experimental brain contusion.

OBJECTIVE: Nitric oxide (NO) and oxygen free radicals are implicated in the pathophysiology of traumatic brain injury (TBI). Peroxynitrite formation from NO and superoxide contributes to secondary neuronal injury but the neuroprotective effects of nitric oxide synthase (NOS)-inhibitors have been contradictory. This study was undertaken to examine whether PTtic administration of the (NOS)-inhibitor N-nitro-l-arginine methyl ester (L-NAME), and a combination of L-NAME and the nitrone radical scavenger 2-sulfo-phenyl-N-tert-butyl nitrone (S-PBN) favorable affects neuronal injury in a model of TBI. METHODS: A weight-drop model of TBI was used. The animals received L-NAME, S-PBN or a combination of the drugs 15 minutes prothrombin time (PT) and sacrificed after 24 hours or six days. NOS activity was measured by the conversion of L-[U-C]arginine to L-[U-C]citrulline. Peroxynitrite formation, cellular apoptosis, neuronal degeneration and survival were assessed by nitrotyrosine-, TUNEL-, Fluoro-Jade- and NeuN-stainings. RESULTS: eNOS and nNOS activity was significantly reduced in animals that received L-NAME alone or the combination with S-PBN. iNOS activity or iNOS immunoreactivity was not affected. All treatments significantly reduced neuronal degeneration and nitrotyrosine immunoreactivity at 24 hours and increased neuronal survival at six days PT. No differences were detected between L-NAME and L-NAME + S-PBN groups. CONCLUSION: NO from NOS contributes to secondary neuronal injury in this TBI-model. PTtic treatment does not inhibit early beneficial NO-related effects. L-NAME and S-PBN limit peroxynitrite formation, promoting neuronal survival. The combination of L-NAME and S-PBN was neuroprotective; surprisingly no additive effects were found on nitrotyrosine formation, apoptosis or neuronal survival.

Animals↗

PubMed2002

Nitric oxide synthase expression after human brain contusion.

OBJECTIVE: Nitric oxide is a universal mediator of biological effects in the brain, and it has been implicated in the pathophysiological processes of traumatic brain injury. Experimental studies have indicated posttraumatic up-regulation of the three different isoforms of nitric oxide synthase (NOS) (i.e., inducible NOS [iNOS], endothelial NOS, and neuronal NOS) after brain trauma. This study was undertaken to investigate the cellular sources and tissue compartments of nitric oxide produced by human patients undergoing surgical treatment for contusional brain injuries. METHODS: Contused brain tissue specimens from eight consecutive patients who underwent surgical treatment for brain contusions 3 hours to 5 days after trauma were evaluated in immunohistochemical analyses. Double-staining assays were used to define which cells produced the different isoforms. RESULTS: Increases in iNOS-positive cells were detectable within 6 hours after trauma, with a peak at 8 to 23 hours. Expression of iNOS after trauma was detected in neurons, macrophages, neutrophils, astrocytes, and oligodendrocytes. The cellular sources of iNOS differed at different times after trauma. No detectable difference in the expression of the neuronal or endothelial isoforms was observed for trauma patients, compared with control subjects. CONCLUSION: iNOS expression was up-regulated in a time-dependent manner in human brain tissue obtained from patients undergoing surgical treatment for contusional trauma. Our human data largely parallel experimental findings in rats, indicating that such trauma models are relevant for experimental studies and treatment trials.

Adolescent↗