The Role of Inducible Nitric Oxide Synthase Following Spinal Cord Injury in Rat

Kwak, Eun Kyoung; Kim, Jung-Wan Martin; Kang, Ku Seong; Lee, Yoon-Hee; Hua, Quan Hong; Park, Tae‐In; Park, Ji Young; Sohn, Yoon Kyung

doi:10.3346/jkms.2005.20.4.663

Cited by 32 publications

(31 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The accuracy of synthetic antisense oligonucleotide probes was confirmed by BLAST searches on NCBI.A 45 base and a 30 base oligonucleotide complementary to exonic mRNA encoding the nNOS and iNOS enzyme (Mineta et al, 2004) 5 0 -gcc ttg ggc atg ctg agg gcc att acc cag acc tgt gac tct gtc-3 0 (Kwak et al, 2005) and iNOS 5 0 -ctg cac cca aac acc aag gt-3 0 as well as a 33 base and 39 base oligonucleotide complementary to exonic mRNA encoding rat GR and MR sequence was also used (McQuade et al, 2004;van Riel et al, 2003). 5 0 -agg aga atc ctc tgc tgc ttg gaa tct gcc tga-3 0 and 5 0 -ttc gga ata gca ccg gaa acg cag ctg acg ttg aca atc t-3 0 .…”

Section: In Situ Hybridizationmentioning

confidence: 99%

Interactions between Nitric Oxide and Corticosterone in the Regulation of Progenitor Cell Proliferation in the Dentate Gyrus of the Adult Rat

Pinnock

Balendra

Chan

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

It is well established that L-NAME, a generic NOS inhibitor, stimulates neurogenesis in the dentate gyrus of the adult rat and corticosterone reduces it. These experiments explore the interaction between L-NAME and corticosterone. L-NAME (50 mg/kg), as expected, increased proliferation, but also lowered plasma corticosterone levels. However, the stimulating action of L-NAME depends on the presence of rhythmic changes in plasma corticosterone, as it is abolished in rats treated with a subcutaneous implant of corticosterone, which flattens the diurnal rhythm. Adrenalectomized rats implanted with corticosterone also failed to respond to L-NAME. Giving them a single daily injection of corticosterone (2 mg/kg) in an attempt to replicate the diurnal rhythm restored the sensitivity of the progenitor cells to L-NAME. The mechanism for this result remains to be investigated. Excess corticosterone given by daily injection (40/mg/kg) reduced proliferation but did not alter the response to L-NAME, even though this occurred from a lower baseline. nNOS was demonstrable only in the inner (proliferative) layer of the dentate gyrus in control rats, and did not alter following excess corticosterone treatment. iNOS was detectable at low levels in control rats, but was increased markedly following corticosterone. eNOS was evident throughout the dentate gyrus, and also increased after corticosterone (particularly in the hilus). Aminoguanidine (100 mg/kg/day; an iNOS antagonist) significantly increased proliferation in corticosterone-treated rats (40 mg/kg/day) but not in controls without additional corticosterone, confirming that iNOS plays a role in corticosterone-regulated neurogenesis. Corticosterone may thus act on progenitor cells in part at least through increased nitric oxide (NO) formation. The effects of reduced NO on neurogenesis may rely on a dual mechanism: corresponding reductions in plasma corticosterone and increased induction of iNOS (and/or eNOS) within the dentate gyrus. The possibility that NO acts downstream of glucocorticoids in the dentate gyrus is suggested.

show abstract

Section: In Situ Hybridizationmentioning

confidence: 99%

Interactions between Nitric Oxide and Corticosterone in the Regulation of Progenitor Cell Proliferation in the Dentate Gyrus of the Adult Rat

Pinnock

Balendra

Chan

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Inflammatory mediators induce NOS-2 expression in astrocyte cultures in vitro (Galea et al 1992;Hewett et al 1993;Simmons and Murphy 1992) and NOS-2 has been detected in astrocytes in several CNS inflammatory conditions in vivo, including cerebral ischemia and Alzheimer and Parkinson diseases (Acarin et al 2002;Endoh et al 1994;Garcion et al 1998;Katsuse et al 2003;Kwak et al 2005;Luth et al 2002). Importantly, NO from glial NOS-2 has been shown to disrupt the blood-brain barrier (Boveri et al 2006) and promote or exacerbate excitotoxic neuronal cell death Hewett et al 1994;Hewett et al 1996;Vidwans and Hewett 2004), an underlying cause of neuropathology in several neurological diseases (Choi 1988;Coyle and Puttfarcken 1993;Meldrum and Garthwaite 1990).…”

mentioning

confidence: 99%

TGFβ1 and TNFα potentiate nitric oxide production in astrocyte cultures by recruiting distinct subpopulations of cells to express NOS-2

Hamby¹,

Gragnolati²,

Hewett³

et al. 2008

Neurochemistry International

View full text Add to dashboard Cite

Nitric oxide (NO) synthase-2 (NOS-2), a key source of NO at sites of neuroinflammation, is induced in astrocyte cultures treated with lipopolysaccharide (LPS) plus interferon-γ (IFNγ). A recent study examining the regulation of astrocytic NOS-2 expression demonstrated that transforming growth factor-β1 (TGFβ1) potentiated LPS plus IFNγ-induced NOS-2 expression via expansion of the pool of astrocytes that express NOS-2. Results in the current report indicate that this population-based mechanism of increasing NOS-2 expression is not restricted to TGFβ1, since it also accounts for the potentiation of NO production in astrocyte cultures by tumor necrosis factor-α (TNFα). In contrast to TGFβ1, which required 24 hr preincubation for optimal potentiation of NO production, TNFα was maximally effective when added concurrently with LPS plus IFNγ. Nevertheless, under conditions that optimally potentiated NO production, both cytokines recruited similar numbers of astrocytes to express NOS-2 (% NOS-2-positive cells after LPS plus IFNγ alone or with TNFα or TGFβ1 was 9.5 ± 1.2, 25.3 ± 2.9, and 32.4 ± 3.0, respectively). Interestingly, stimulation of astrocytes in the presence of both TGFβ1 and TNFα additively increased the number of astrocytes that expressed NOS-2 protein (% NOS-2-positive cells was 61.0 ± 4.2) relative to each cytokine alone. Potentiation of NO production by either TNFα or TGFβ1 was not ablated by neutralizing antibodies to TGFβ1 or TNFα, respectively. Thus, the two cytokines act independently to recruit separate pools of astrocytes to express NOS-2. These results are consistent with the notion that astrocytes possess an innate heterogeneity with respect to responsiveness to these cytokines. KeywordsLPS; cytokines; heterogeneity; NO; iNOS; nitric oxide synthase Nitric oxide (NO) is an endogenously derived free radical gas that affects a spectrum of homeostatic and physiologic processes, including blood flow and coagulation, normal brain and heart function, and innate immunity (Belge et al. 2005;Ignarro et al. 1999;MacMicking et al. 1997;Yun et al. 1996). However, it can be harmful under certain pathophysiological conditions. Within the CNS, aberrant NO production has been linked to cerebrovascular dysfunction ( Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NO is derived from L-arginine by the catalytic action of three different NOS isoforms (Stuehr 1999). NOS-1 and -3 are constitutively expressed in neurons and endothelial cells, respectively, and thus were initially termed nNOS and eNOS. In contrast, NOS-2 is not constitutively expressed but can be induced ...

show abstract

“…This could be a result of the OECs inducing the differentiation of stem cells into functional neurons and the modulation of early neuroinflammatory response. 27,28 We also noticed that scar bridging was more explicit in OEC-engrafted mice. It is evident from Figure 4 that LPtransplanted OECs accelerate scar bridging.…”

mentioning

confidence: 67%

Intrathecal transplantation of olfactory ensheathing cells by lumbar puncture for thoracic spinal cord injury in mice

Liu¹,

Ji²,

S³

et al. 2017

View full text Add to dashboard Cite

*These authors contributed equally to this workObjectives: To investigate the distribution and function of olfactory ensheathing cells (OECs) following lumbar puncture (LP) transplantation in mouse spinal cord injury (SCI). Methods: OECs were transplanted by LP at level L3-5, 1 week after transected SCI at T8 vertebra. Mice were killed at 3, 21, and 56 days after LP transplantation, and the relative distribution of cells at T8 vertebra was quantitated. The injured spine was also tested by immunohistochemistry to assess neuron regeneration and scar bridging at 8 weeks posttransplantation. Motor functions of mice were evaluated during the observation period using the Basso Mouse Scale. Results: OECs were examined and confirmed by studying cell morphology under phase contrast and immunostaining of NGFR p75. LP-transplanted OECs could be detected just 3 days after transplantation (p75 + area: 0.16 mm 2 ) and accumulated to 0.31 and 0.30 mm 2 at 21 and 56 days postengraftment, respectively. The number of endogenous neurons, −400 to +400 µm, far from the epicenter, in OEC-transplanted mice was more than that in SCI mice without engraftment. SCI lesion of mice in the control group (164.3±3.97 µm) was much longer than that in OECgrafted group (116.7±3.60 µm). Grafts of OECs induced significant functional improvement in mice that underwent T8 vertebral transection, just from 3 days after cell injection. Conclusion: LP is a minimally invasive method for OEC transplantation to treat SCI. This is the first study to visualize the distribution and functions of LP-transplanted OECs in the intact and injured spinal cord.

show abstract

The Role of Inducible Nitric Oxide Synthase Following Spinal Cord Injury in Rat

Cited by 32 publications

References 19 publications

Interactions between Nitric Oxide and Corticosterone in the Regulation of Progenitor Cell Proliferation in the Dentate Gyrus of the Adult Rat

Interactions between Nitric Oxide and Corticosterone in the Regulation of Progenitor Cell Proliferation in the Dentate Gyrus of the Adult Rat

TGFβ1 and TNFα potentiate nitric oxide production in astrocyte cultures by recruiting distinct subpopulations of cells to express NOS-2

Intrathecal transplantation of olfactory ensheathing cells by lumbar puncture for thoracic spinal cord injury in mice

Contact Info

Product

Resources

About