A study of experimental autoimmune encephalomyelitis in dogs as a disease model for canine necrotizing encephalitis

Moon, Jong-Hyun; Jung, Han‐Sung; Lee, Hee-Chun; Jeon, Joon-Hyeok; Kim, Nahyun; Sur, Jung-Hyang; Ha, Jung Min; Jung, Dong‐In

doi:10.4142/jvs.2015.16.2.203

Cited by 11 publications

(23 citation statements)

References 26 publications

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“…However, EAE does not reproduce all clinical, pathological, or immunological features of human disease [48]. Canine MUO may be useful as a naturally occurring model of MS, given neuroimmunological similarities of these diseases, including the upregulation of IFNγ, IL-17, and MHC-II expression in the nervous system [5,7,34,[49][50][51]. Moreover, the genetic association of MHC-II found in dogs with MUO is present in MS [7].…”

Section: Discussionmentioning

confidence: 99%

Placenta-derived multipotent mesenchymal stromal cells: a promising potential cell-based therapy for canine inflammatory brain disease

et al. 2020

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Background Canine inflammatory brain disease (IBD) is a severe inflammatory disorder characterized by infiltration of activated immune cell subsets into the brain and spinal cord. Multipotent mesenchymal stromal cells (MSCs) are a promising therapy for IBD, based on their potent pro-angiogenic, neuroprotective, and immunomodulatory properties. The aims of this study were to compare the immunomodulatory attributes of canine adipose-derived MSCs (ASCs) and placenta-derived MSCs (PMSCs) in vitro. These data will serve as potency information to help inform the optimal MSC cell source to treat naturally occurring canine IBD. Methods Indoleamine 2,3 dioxygenase (IDO) activity and prostaglandin E 2 (PGE 2 ) concentration at baseline and after stimulation with interferon gamma (IFNγ) and/or tumor necrosis factor alpha (TNFα) were measured from canine ASC and PMSC cultures. Leukocyte suppression assays (LSAs) were performed to compare the ability of ASCs and PMSCs to inhibit activated peripheral blood mononuclear cell (PBMC) proliferation. IDO activity and PGE 2 ; interleukin (IL)-2, IL-6, and IL-8; TNFα; and vascular endothelial growth factor (VEGF) concentrations were also measured from co-culture supernatants. Cell cycle analysis was performed to determine how ASCs and PMSCs altered lymphocyte proliferation. Results Activated canine MSCs from both tissue sources secreted high concentrations of IDO and PGE 2 , after direct stimulation with IFNγ and TNFα, or indirect stimulation by activated PBMCs. Both ASCs and PMSCs inhibited activated PBMC proliferation in LSA assays; however, PMSCs inhibited PBMC proliferation significantly more than ASCs. Blocking PGE 2 and IDO in LSA assays determined that PGE 2 is important only for ASC inhibition of PBMC proliferation. Activated ASCs increased IL-6 and VEGF secretion and decreased TNFα secretion, while activated PMSCs increased IL-6, IL-8, and VEGF secretion. ASCs inhibited lymphocyte proliferation via cell cycle arrest in the G0/G1 and PMSCs inhibited lymphocyte proliferation via induction of lymphocyte apoptosis. Conclusion Our results demonstrate that ASCs and PMSCs have substantial in vitro potential as a cell-based therapy for IBD; however, PMSCs more potently inhibited lymphocyte proliferation by inducing apoptosis of activated lymphocytes. These data suggest that the mechanism by which ASCs and PMSCs downregulate PBMC proliferation differs. Additional studies may elucidate additional mechanisms by which canine MSCs modulate neuroinflammatory responses.

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Section: Discussionmentioning

confidence: 99%

Placenta-derived multipotent mesenchymal stromal cells: a promising potential cell-based therapy for canine inflammatory brain disease

et al. 2020

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“…TKs play a key role in this immune-related process of MS, and clinical trials have assessed the efficacy of blocking TKs in MS treatment [12]. Recently, MS was considered neuropathologically similar to GME, which is considered a T-cellrelated autoimmune CNS disorder, in dogs [1,13,14].…”

Section: Discussionmentioning

confidence: 99%

Use of imatinib mesylate in a dog with meningoencephalitis of unknown etiology

Song¹,

Jung²

2020

J Biomed Transl Res

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A 4-year-old, female, Maltese dog with bilateral hind limb ataxia was brought to Gyeongsang National University Animal Medical Center (GAMC). Based on the previous medical and imaging records, the patient was presumptively diagnosed with a primary brain tumor of the right temporo-occipital lobe on magnetic resonance imaging (MRI) in a local animal hospital. Hydroxyurea and prednisolone therapy was initiated, and the neurological signs transiently improved. Approximately 5 months after the treatment, ataxia recurred and the patient was referred to GAMC. Upon admission, MRI at the same anatomic level as in the previous MRI was performed. Results showed inflammatory brain lesions, not brain neoplastic changes. Considering this finding, the dog was tentatively diagnosed with meningoencephalitis of unknown etiology (MUE). We added oral imatinib mesylate (10 mg/kg every 24 h), and the dosage of prednisolone was increased to 1 mg/kg twice daily. Hydroxyurea was discontinued. A rapid improvement in neurological signs was observed after the initiation of imatinib mesylate treatment. Approximately 2 months after the treatment, the size of the inflammatory lesion remarkably decreased on repeat MRI. The patient had been doing well, and there were no overt neurological signs 259 days after the initiation of imatinib mesylate therapy. We describe a case of MUE in a dog that was successfully managed with imatinib mesylate.

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“…Glucocorticoid suspensions are known to induce local or diffuse cerebral meningitis and arachnoiditis. In some serious cases, glucocorticoid suspensions may induce separation of the central ventricle or spinal cord aqueduct, which will lead to fatal intracranial hypertension [9]. Different agents of vitamin B 12 are used to inject into epidural space; however, it is unknown what would happen if vitamin B 12 was injected into the cerebrospinal fluid [10].…”

Section: Discussionmentioning

confidence: 99%

Inadvertent Application of a Drug Mixture into the Subarachnoid Space When Performing an Outward-Going Lumbar Intervertebral Foramina Injection

Nie¹

2016

WJNS

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An outward-going intervertebral foramina puncture along the side of lumbar vertebra spinous process was used to avoid infusing drugs into the subarachnoid space. However, we still had an inadvertent malpractice. The patient was diagnosed with lumbar discogenic lower back pain and was administrated an outward-going intervertebral foramina puncture through the side of lumbar vertebra spinous process (L5-S1). The drug mixture, containing triamcinolone acetonide suspension, cyanocobalamin and bupivacaine HCl, was injected. The patient had palpitations, chest tightness, dyspnea, bradycardia, and hypotension 3 min right after the injection. The vital signs gradually stabilized after treatment with atropine sulfate; however, he had complete sensorimotor loss below the level of distribution of the T2 spinal nerve. The cerebrospinal fluid pressure was lower in the subarachnoid space and the cerebrospinal fluid was slightly turbid and light pink in color. Six hours later, the sensory, motor, defecation, and urination functions returned to normal level. The patient had follow-up evaluations at 1, 3, and 6 months. The lumbar and hip pain was mild-to-severe at times as usual, but there were no other neurologic sequelae. Conclusions: This case showed that there is a risk that drugs may stray into the subarachnoid space during an outward-going intervertebral foramina puncture through the side of lumbar vertebral spinous process. The complication may occur due to a distal nerve root cyst. The result of triamcinolone acetonide suspension and cyanocobalamin injection into the cerebrospinal fluid was not as serious as we imagined.

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A study of experimental autoimmune encephalomyelitis in dogs as a disease model for canine necrotizing encephalitis

Cited by 11 publications

References 26 publications

Placenta-derived multipotent mesenchymal stromal cells: a promising potential cell-based therapy for canine inflammatory brain disease

Placenta-derived multipotent mesenchymal stromal cells: a promising potential cell-based therapy for canine inflammatory brain disease

Use of imatinib mesylate in a dog with meningoencephalitis of unknown etiology

Inadvertent Application of a Drug Mixture into the Subarachnoid Space When Performing an Outward-Going Lumbar Intervertebral Foramina Injection

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