Microglia-Induced Maladaptive Plasticity Can Be Modulated by Neuropeptides In Vivo

Table 1

In vivo administration of neuropeptides in the central nervous system produces beneficial effects in experimental models of brain diseases.

Neuropeptide	Experimental model	Delivery method/place	Administration: single/chronic	Administration timing	Effects on pathology (1), microglia (2) [timing of assessment]	Ref.
VIP	Brain trauma: vertical stab wound operation in periventricular area by glass micropipette	Micropipette/the same place as trauma	Single	The same time as trauma	(1) Reduced neuronal cell loss and inflammatory cytokine expression,; (2) reduced microglia activation (CD11b/Mac1 expression) 5 days]	[108]
VIP	MPTP toxicity (Parkinson’s disease model)	Micropipette? (not described)/substantia nigra	Single	One hour after i.p. injection of MPTP	(1) Reduced nigro-striatal dopaminergic neuron loss [7 days] and inflammatory cytokine/iNOS expression [12 hrs],; (2) reduced microglia activation (CD11b/Mac1 expression) [24 hrs]	[109]
PACAP (+hMSCs)	Spinal cord injury (by weight drop device, 127)	Microsyringe (31-gauge needle)/spinal cord	Single	7 days after injury (the same time for PACAP and hMSCs)	(1) Increased motor functional recovery [31 days],; (2) increased sparing of fibers [31 days],; (3) increased level of antioxidant enzymes [7? 14? days]	[128]
PACAP	Permanent focal ischemia	Transplanted PACAP-producing stem cells/i.c.v.	Chronic PACAP production	Transplant: 3 days after ischemia	(1) Decreased neurological severity score [7, 14 days],; (2) increased motor coordination [7, 14 days],; (3) increased anti-inflammatory and decreased proinflammatory cytokines [7 days],; (4) microglia: decreased cell number, increased ramification, Arg-1 and Ym-1 expression [7 days]	[129]
CGRP	EAE (MS model)	Osmotic minipumps/intrathecal (lumbar CSF)	Chronic	2 days after immunization	(1) Decreased motor impairment score,; (2) microglia: decreased morphological activation, increased nuclear localization of a receptor component protein 15 days]	[81]
Apelin-13	Transient focal ischemia/reperfusion (stroke model)	i.c.v.	Single	The same time as reperfusion	(1) Decreased neurological score, reduction of infarct volume, decreased myeloperoxidase activity, decreased inflammatory markers,; (2) decreased microglia cell number 24 hrs]	[185]

MPTP: 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine; hMSCs: human mesenchymal stem cells; i.c.v.: intracerebroventricularly; EAE: experimental autoimmune encephalomyelitis; MS: multiple sclerosis; CSF: cerebrospinal fluid.