Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2018

Open Access 01-12-2018 | Research

Laquinimod protects the optic nerve and retina in an experimental autoimmune encephalomyelitis model

Authors: Anna T. Wilmes, Sabrina Reinehr, Sandra Kühn, Xiomara Pedreiturria, Laura Petrikowski, Simon Faissner, Ilya Ayzenberg, Gesa Stute, Ralf Gold, H. Burkhard Dick, Ingo Kleiter, Stephanie C. Joachim

Published in: Journal of Neuroinflammation | Issue 1/2018

Login to get access

Abstract

Background

The oral immunomodulatory agent laquinimod is currently evaluated for multiple sclerosis (MS) treatment. Phase II and III studies demonstrated a reduction of degenerative processes. In addition to anti-inflammatory effects, laquinimod might have neuroprotective properties, but its impact on the visual system, which is often affected by MS, is unknown. The aim of our study was to investigate potential protective effects of laquinimod on the optic nerve and retina in an experimental autoimmune encephalomyelitis (EAE) model.

Methods

We induced EAE in C57/BL6 mice via MOG35–55 immunization. Animals were divided into an untreated EAE group, three EAE groups receiving laquinimod (1, 5, or 25 mg/kg daily), starting the day post-immunization, and a non-immunized control group. Thirty days post-immunization, scotopic electroretinograms were carried out, and mice were sacrificed for histopathology (HE, LFB), immunohistochemistry (MBP, Iba1, Tmem119, F4/80, GFAP, vimentin, Brn-3a, cleaved caspase 3) of the optic nerve and retina, and retinal qRT-PCR analyses (Brn-3a, Iba1, Tmem119, AMWAP, CD68, GFAP). To evaluate the effect of a therapeutic approach, EAE animals were treated with 25 mg/kg laquinimod from day 16 when 60% of the animals had developed clinical signs of EAE.

Results

Laquinimod reduced neurological EAE symptoms and improved the neuronal electrical output of the inner nuclear layer compared to untreated EAE mice. Furthermore, cellular infiltration, especially recruited phagocytes, and demyelination in the optic nerve were reduced. Microglia were diminished in optic nerve and retina. Retinal macroglial signal was reduced under treatment, whereas in the optic nerve macroglia were not affected. Additionally, laquinimod preserved retinal ganglion cells and reduced apoptosis. A later treatment with laquinimod in a therapeutic approach led to a reduction of clinical signs and to an improved b-wave amplitude. However, no changes in cellular infiltration and demyelination of the optic nerves were observed. Also, the number of retinal ganglion cells remained unaltered.

Conclusion

From our study, we deduce neuroprotective and anti-inflammatory effects of laquinimod on the optic nerve and retina in EAE mice, when animals were treated before any clinical signs were noted. Given the fact that the visual system is frequently affected by MS, the agent might be an interesting subject of further neuro-ophthalmic investigations.
Appendix
Available only for authorised users
Literature
1.
Kawachi I, Lassmann H. Neurodegeneration in multiple sclerosis and neuromyelitis optica. J Neurol Neurosurg Psychiatry. 2017;88:137–45.CrossRefPubMed
2.
Runia TF, van Pelt-Gravesteijn ED, Hintzen RQ. Recent gains in clinical multiple sclerosis research. CNS Neurol Disord Drug Targets. 2012;11:497–505.CrossRefPubMed
3.
Olsson T, Barcellos LF, Alfredsson L. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nat Rev Neurol. 2017;13:25–36.CrossRefPubMed
4.
Stadelmann C, Wegner C, Bruck W. Inflammation, demyelination, and degeneration - recent insights from MS pathology. Biochim Biophys Acta. 2011;1812:275–82.CrossRefPubMed
5.
6.
Gelfand JM. Multiple sclerosis: diagnosis, differential diagnosis and clinical presentation. In: Goodin DS, editor. Handbook of Clinical Neurology, vol. 122. Amsterdam: Elsevier; 2014. p. 269–90. [Aminoff MJ, Boller F, Swaab DF (Series Editor): Multiple sclerosis and related disorders].
7.
Ziemssen T, Wilhelm H, Ziemssen F. Multiple sclerosis: an update with practical guidelines for ophthalmologists. Ophthalmologe. 2006;103:621–43.CrossRefPubMed
8.
Lampert EJ, Andorra M, Torres-Torres R, Ortiz-Perez S, Llufriu S, Sepulveda M, Sola N, Saiz A, Sanchez-Dalmau B, Villoslada P, Martinez-Lapiscina EH. Color vision impairment in multiple sclerosis points to retinal ganglion cell damage. J Neurol. 2015;262:2491–7.CrossRefPubMed
9.
10.
Sabadia SB, Nolan RC, Galetta KM, Narayana KM, Wilson JA, Calabresi PA, Frohman EM, Galetta SL, Balcer LJ. 20/40 or better visual acuity after optic neuritis: not as good as we once thought? J Neuroophthalmol. 2016;36:369–76.CrossRefPubMed
11.
Jenkins TM, Toosy AT. Optic neuritis: the eye as a window to the brain. Curr Opin Neurol. 2017;30:61–6.CrossRefPubMed
12.
Ben-Nun A, Kaushansky N, Kawakami N, Krishnamoorthy G, Berer K, Liblau R, Hohlfeld R, Wekerle H. From classic to spontaneous and humanized models of multiple sclerosis: impact on understanding pathogenesis and drug development. J Autoimmun. 2014;54:33–50.CrossRefPubMed
13.
Gold R, Linington C, Lassmann H. Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain. 2006;129:1953–71.CrossRefPubMed
14.
Guy J. Optic nerve degeneration in experimental autoimmune encephalomyelitis. Ophthalmic Res. 2008;40:212–6.CrossRefPubMed
15.
Horstmann L, Schmid H, Heinen AP, Kurschus FC, Dick HB, Joachim SC. Inflammatory demyelination induces glia alterations and ganglion cell loss in the retina of an experimental autoimmune encephalomyelitis model. J Neuroinflammation. 2013;10:120.CrossRefPubMedPubMedCentral
16.
Tian AY, Zhang RW, Shi XG, Yu HM. Alteration of T helper cell subsets in the optic nerve of experimental autoimmune encephalomyelitis. Int J Mol Med. 2010;25:869–74.CrossRefPubMed
17.
Horstmann L, Kuehn S, Pedreiturria X, Haak K, Pfarrer C, Dick HB, Kleiter I, Joachim SC. Microglia response in retina and optic nerve in chronic experimental autoimmune encephalomyelitis. J Neuroimmunol. 2016;298:32–41.CrossRefPubMed
18.
Nicholas R, Giannetti P, Alsanousi A, Friede T, Muraro PA. Development of oral immunomodulatory agents in the management of multiple sclerosis. Drug Des Devel Ther. 2011;5:255–74.CrossRefPubMedPubMedCentral
19.
Jansson K, Fristedt T, Olsson A, Svensson B, Jonsson S. Synthesis and reactivity of laquinimod, a quinoline-3-carboxamide: intramolecular transfer of the enol proton to a nitrogen atom as a plausible mechanism for ketene formation. J Org Chem. 2006;71:1658–67.CrossRefPubMed
20.
Brunmark C, Runstrom A, Ohlsson L, Sparre B, Brodin T, Astrom M, Hedlund G. The new orally active immunoregulator laquinimod (ABR-215062) effectively inhibits development and relapses of experimental autoimmune encephalomyelitis. J Neuroimmunol. 2002;130:163–72.CrossRefPubMed
21.
Runstrom A, Leanderson T, Ohlsson L, Axelsson B. Inhibition of the development of chronic experimental autoimmune encephalomyelitis by laquinimod (ABR-215062) in IFN-beta k.o. and wild type mice. J Neuroimmunol. 2006;173:69–78.CrossRefPubMed
22.
Pitarokoili K, Ambrosius B, Schrewe L, Hayardeny L, Hayden M, Gold R. Laquinimod exerts strong clinical and immunomodulatory effects in Lewis rat experimental autoimmune neuritis. J Neuroimmunol. 2014;274:38–45.CrossRefPubMed
23.
Comi G, Jeffery D, Kappos L, Montalban X, Boyko A, Rocca MA, Filippi M. Placebo-controlled trial of oral laquinimod for multiple sclerosis. N Engl J Med. 2012;366:1000–9.CrossRefPubMed
24.
Filippi M, Rocca MA, Pagani E, De Stefano N, Jeffery D, Kappos L, Montalban X, Boyko AN, Comi G. Placebo-controlled trial of oral laquinimod in multiple sclerosis: MRI evidence of an effect on brain tissue damage. J Neurol Neurosurg Psychiatry. 2014;85:851–8.CrossRefPubMed
25.
Vollmer TL, Sorensen PS, Selmaj K, Zipp F, Havrdova E, Cohen JA, Sasson N, Gilgun-Sherki Y, Arnold DL. A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis. J Neurol. 2014;261:773–83.CrossRefPubMed
26.
Kleiter I, Song J, Lukas D, Hasan M, Neumann B, Croxford AL, Pedre X, Hovelmeyer N, Yogev N, Mildner A, et al. Smad7 in T cells drives T helper 1 responses in multiple sclerosis and experimental autoimmune encephalomyelitis. Brain. 2010;133:1067–81.CrossRefPubMedPubMedCentral
27.
Enders U, Lobb R, Pepinsky RB, Hartung HP, Toyka KV, Gold R. The role of the very late antigen-4 and its counterligand vascular cell adhesion molecule-1 in the pathogenesis of experimental autoimmune neuritis of the Lewis rat. Brain. 1998;121:1257–66.CrossRefPubMed
28.
Schmid H, Renner M, Dick HB, Joachim SC. Loss of inner retinal neurons after retinal ischemia in rats. Invest Ophthalmol Vis Sci. 2014;55:2777–87.CrossRefPubMed
29.
30.
Joachim SC, Gramlich OW, Laspas P, Schmid H, Beck S, von Pein HD, Dick HB, Pfeiffer N, Grus FH. Retinal ganglion cell loss is accompanied by antibody depositions and increased levels of microglia after immunization with retinal antigens. PLoS One. 2012;7:e40616.CrossRefPubMedPubMedCentral
31.
Reinehr S, Kuehn S, Casola C, Koch D, Stute G, Grotegut P, Dick HB, Joachim SC. HSP27 immunization reinforces AII amacrine cell and synapse damage induced by S100 in an autoimmune glaucoma model. Cell Tissue Res. 2018;371(2):237–49.
32.
Noristani R, Kuehn S, Stute G, Reinehr S, Stellbogen M, Dick HB, Joachim SC. Retinal and optic nerve damage is associated with early glial responses in an experimental autoimmune glaucoma model. J Mol Neurosci. 2016;58:470–82.CrossRefPubMed
33.
Reinehr S, Reinhard J, Gandej M, Kuehn S, Noristani R, Faissner A, Dick HB, Joachim SC. Simultaneous complement response via lectin pathway in retina and optic nerve in an experimental autoimmune glaucoma model. Front Cell Neurosci. 2016;10:140.CrossRefPubMedPubMedCentral
34.
Pfaffl MW, Horgan GW, Dempfle L. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 2002;30:e36.CrossRefPubMedPubMedCentral
35.
Bennett ML, Bennett FC, Liddelow SA, Ajami B, Zamanian JL, Fernhoff NB, Mulinyawe SB, Bohlen CJ, Adil A, Tucker A, et al. New tools for studying microglia in the mouse and human CNS. Proc Natl Acad Sci U S A. 2016;113:E1738–46.CrossRefPubMedPubMedCentral
36.
Karlstetter M, Walczak Y, Weigelt K, Ebert S, Van den Brulle J, Schwer H, Fuchshofer R, Langmann T. The novel activated microglia/macrophage WAP domain protein, AMWAP, acts as a counter-regulator of proinflammatory response. J Immunol. 2010;185:3379–90.CrossRefPubMed
37.
Karlstetter M, Sorusch N, Caramoy A, Dannhausen K, Aslanidis A, Fauser S, Boesl MR, Nagel-Wolfrum K, Tamm ER, Jagle H, et al. Disruption of the retinitis pigmentosa 28 gene Fam161a in mice affects photoreceptor ciliary structure and leads to progressive retinal degeneration. Hum Mol Genet. 2014;23:5197–210.CrossRefPubMed
38.
Scholz R, Caramoy A, Bhuckory MB, Rashid K, Chen M, Xu H, Grimm C, Langmann T. Targeting translocator protein (18 kDa) (TSPO) dampens pro-inflammatory microglia reactivity in the retina and protects from degeneration. J Neuroinflammation. 2015;12:201.CrossRefPubMedPubMedCentral
39.
Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol. 2000;47:707–17.CrossRefPubMed
40.
Rasmussen S, Wang Y, Kivisakk P, Bronson RT, Meyer M, Imitola J, Khoury SJ. Persistent activation of microglia is associated with neuronal dysfunction of callosal projecting pathways and multiple sclerosis-like lesions in relapsing—remitting experimental autoimmune encephalomyelitis. Brain. 2007;130:2816–29.CrossRefPubMed
41.
Aharoni R, Saada R, Eilam R, Hayardeny L, Sela M, Arnon R. Oral treatment with laquinimod augments regulatory T-cells and brain-derived neurotrophic factor expression and reduces injury in the CNS of mice with experimental autoimmune encephalomyelitis. J Neuroimmunol. 2012;251:14–24.CrossRefPubMed
42.
Wegner C, Stadelmann C, Pfortner R, Raymond E, Feigelson S, Alon R, Timan B, Hayardeny L, Bruck W. Laquinimod interferes with migratory capacity of T cells and reduces IL-17 levels, inflammatory demyelination and acute axonal damage in mice with experimental autoimmune encephalomyelitis. J Neuroimmunol. 2010;227:133–43.CrossRefPubMed
43.
Yang JS, Xu LY, Xiao BG, Hedlund G, Link H. Laquinimod (ABR-215062) suppresses the development of experimental autoimmune encephalomyelitis, modulates the Th1/Th2 balance and induces the Th3 cytokine TGF-beta in Lewis rats. J Neuroimmunol. 2004;156:3–9.CrossRefPubMed
44.
Zilkha-Falb R, Gurevich M, Hayardeny L, Achiron A. The role of laquinimod in modulation of the immune response in relapsing-remitting multiple sclerosis: lessons from gene expression signatures. J Neuroimmunol. 2015;283:11–6.CrossRefPubMed
45.
Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science. 2005;308:1314–8.CrossRefPubMed
46.
Ransohoff RM, Cardona AE. The myeloid cells of the central nervous system parenchyma. Nature. 2010;468:253–62.CrossRefPubMed
47.
Hobom M, Storch MK, Weissert R, Maier K, Radhakrishnan A, Kramer B, Bahr M, Diem R. Mechanisms and time course of neuronal degeneration in experimental autoimmune encephalomyelitis. Brain Pathol. 2004;14:148–57.CrossRefPubMed
48.
49.
Takeuchi H, Jin S, Wang J, Zhang G, Kawanokuchi J, Kuno R, Sonobe Y, Mizuno T, Suzumura A. Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner. J Biol Chem. 2006;281:21362–8.CrossRefPubMed
50.
Nikic I, Merkler D, Sorbara C, Brinkoetter M, Kreutzfeldt M, Bareyre FM, Bruck W, Bishop D, Misgeld T, Kerschensteiner M. A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat Med. 2011;17:495–9.CrossRefPubMed
51.
Girolamo F, Ferrara G, Strippoli M, Rizzi M, Errede M, Trojano M, Perris R, Roncali L, Svelto M, Mennini T, Virgintino D. Cerebral cortex demyelination and oligodendrocyte precursor response to experimental autoimmune encephalomyelitis. Neurobiol Dis. 2011;43:678–89.CrossRefPubMed
52.
Kooi EJ, Strijbis EM, van der Valk P, Geurts JJ. Heterogeneity of cortical lesions in multiple sclerosis: clinical and pathologic implications. Neurology. 2012;79:1369–76.CrossRefPubMed
53.
Magliozzi R, Howell OW, Reeves C, Roncaroli F, Nicholas R, Serafini B, Aloisi F, Reynolds R. A gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol. 2010;68:477–93.CrossRefPubMed
54.
Satoh J, Kino Y, Asahina N, Takitani M, Miyoshi J, Ishida T, Saito Y. TMEM119 marks a subset of microglia in the human brain. Neuropathology. 2016;36:39–49.CrossRefPubMed
55.
Zrzavy T, Hametner S, Wimmer I, Butovsky O, Weiner HL, Lassmann H. Loss of ‘homeostatic’ microglia and patterns of their activation in active multiple sclerosis. Brain. 2017;140:1900–13.CrossRefPubMedPubMedCentral
56.
Mishra MK, Wang J, Keough MB, Fan Y, Silva C, Sloka S, Hayardeny L, Bruck W, Yong VW. Laquinimod reduces neuroaxonal injury through inhibiting microglial activation. Ann Clin Transl Neurol. 2014;1:409–22.CrossRefPubMedPubMedCentral
57.
Thone J, Ellrichmann G, Seubert S, Peruga I, Lee DH, Conrad R, Hayardeny L, Comi G, Wiese S, Linker RA, Gold R. Modulation of autoimmune demyelination by laquinimod via induction of brain-derived neurotrophic factor. Am J Pathol. 2012;180:267–74.CrossRefPubMed
58.
Ruffini F, Rossi S, Bergamaschi A, Brambilla E, Finardi A, Motta C, Studer V, Barbieri F, De Chiara V, Hayardeny L, et al. Laquinimod prevents inflammation-induced synaptic alterations occurring in experimental autoimmune encephalomyelitis. Mult Scler. 2013;19:1084–94.CrossRefPubMed
59.
Moore S, Khalaj AJ, Yoon J, Patel R, Hannsun G, Yoo T, Sasidhar M, Martinez-Torres L, Hayardeny L, Tiwari-Woodruff SK. Therapeutic laquinimod treatment decreases inflammation, initiates axon remyelination, and improves motor deficit in a mouse model of multiple sclerosis. Brain Behav. 2013;3:664–82.CrossRefPubMedPubMedCentral
60.
Sun D, Jakobs TC. Structural remodeling of astrocytes in the injured CNS. Neuroscientist. 2012;18:567–88.CrossRefPubMed
61.
62.
Pekny M, Eliasson C, Chien CL, Kindblom LG, Liem R, Hamberger A, Betsholtz C. GFAP-deficient astrocytes are capable of stellation in vitro when cocultured with neurons and exhibit a reduced amount of intermediate filaments and an increased cell saturation density. Exp Cell Res. 1998;239:332–43.CrossRefPubMed
63.
Mayo L, Trauger SA, Blain M, Nadeau M, Patel B, Alvarez JI, Mascanfroni ID, Yeste A, Kivisakk P, Kallas K, et al. Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation. Nat Med. 2014;20:1147–56.CrossRefPubMedPubMedCentral
64.
Bruck W, Pfortner R, Pham T, Zhang J, Hayardeny L, Piryatinsky V, Hanisch UK, Regen T, van Rossum D, Brakelmann L, et al. Reduced astrocytic NF-kappaB activation by laquinimod protects from cuprizone-induced demyelination. Acta Neuropathol. 2012;124:411–24.CrossRefPubMedPubMedCentral
65.
Nakazawa T, Takeda M, Lewis GP, Cho KS, Jiao J, Wilhelmsson U, Fisher SK, Pekny M, Chen DF, Miller JW. Attenuated glial reactions and photoreceptor degeneration after retinal detachment in mice deficient in glial fibrillary acidic protein and vimentin. Invest Ophthalmol Vis Sci. 2007;48:2760–8.CrossRefPubMedPubMedCentral
66.
Fairless R, Williams SK, Hoffmann DB, Stojic A, Hochmeister S, Schmitz F, Storch MK, Diem R. Preclinical retinal neurodegeneration in a model of multiple sclerosis. J Neurosci. 2012;32:5585–97.CrossRefPubMed
67.
Guan Y, Shindler KS, Tabuena P, Rostami AM. Retinal ganglion cell damage induced by spontaneous autoimmune optic neuritis in MOG-specific TCR transgenic mice. J Neuroimmunol. 2006;178:40–8.CrossRefPubMed
68.
Shindler KS, Ventura E, Dutt M, Rostami A. Inflammatory demyelination induces axonal injury and retinal ganglion cell apoptosis in experimental optic neuritis. Exp Eye Res. 2008;87:208–13.CrossRefPubMedPubMedCentral
69.
Lidster K, Jackson SJ, Ahmed Z, Munro P, Coffey P, Giovannoni G, Baker MD, Baker D. Neuroprotection in a novel mouse model of multiple sclerosis. PLoS One. 2013;8:e79188.CrossRefPubMedPubMedCentral
70.
Saidha S, Syc SB, Ibrahim MA, Eckstein C, Warner CV, Farrell SK, Oakley JD, Durbin MK, Meyer SA, Balcer LJ, et al. Primary retinal pathology in multiple sclerosis as detected by optical coherence tomography. Brain. 2011;134:518–33.CrossRefPubMed
71.
Brambilla R, Dvoriantchikova G, Barakat D, Ivanov D, Bethea JR, Shestopalov VI. Transgenic inhibition of astroglial NF-kappaB protects from optic nerve damage and retinal ganglion cell loss in experimental optic neuritis. J Neuroinflammation. 2012;9:213.CrossRefPubMedPubMedCentral
72.
Green AJ, McQuaid S, Hauser SL, Allen IV, Lyness R. Ocular pathology in multiple sclerosis: retinal atrophy and inflammation irrespective of disease duration. Brain. 2010;133:1591–601.CrossRefPubMedPubMedCentral
73.
Bruck W, Wegner C. Insight into the mechanism of laquinimod action. J Neurol Sci. 2011;306:173–9.CrossRefPubMed
Metadata
Title
Laquinimod protects the optic nerve and retina in an experimental autoimmune encephalomyelitis model
Authors
Anna T. Wilmes
Sabrina Reinehr
Sandra Kühn
Xiomara Pedreiturria
Laura Petrikowski
Simon Faissner
Ilya Ayzenberg
Gesa Stute
Ralf Gold
H. Burkhard Dick
Ingo Kleiter
Stephanie C. Joachim
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2018
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-018-1208-3

Other articles of this Issue 1/2018

Journal of Neuroinflammation 1/2018 Go to the issue

Research

LncRNA H19 contributes to hippocampal glial cell activation via JAK/STAT signaling in a rat model of temporal lobe epilepsy

Research

Longitudinal chemokine profile expression in a blood-brain barrier model from Alzheimer transgenic versus wild-type mice

Research

Reduced ex vivo release of pro-inflammatory cytokines and elevated plasma interleukin-6 are inflammatory signatures of post-stroke delirium

Research

Splenic involvement in umbilical cord matrix-derived mesenchymal stromal cell-mediated effects following traumatic spinal cord injury

Research

Neuregulin-1 attenuates experimental cerebral malaria (ECM) pathogenesis by regulating ErbB4/AKT/STAT3 signaling

Research

Prostaglandin D2/J2 signaling pathway in a rat model of neuroinflammation displaying progressive parkinsonian-like pathology: potential novel therapeutic targets