Table 2.

Summary of safety assessments conducted by included protocols.

In Vivo Subject	Study Reference	Safety Assessments
		Macroscopic				Histological									Biochemical	Electrophysiological	Physical/Behvaioural
		MRI	PET	ΔT	Gross	H/E	TUNEL	VF	LB	CV	PB	GFAP	Iba1	Other
Mouse	[38]	X				X
	[73]	X			X	X
	[39]					X
	[74]					X
	[67]					X
	[75]					X
	[76]					X
	[60]					X	X
	[77]	X				X
	[68]					X
	[78]	X				X											X
	[61]											X	X	X	X (PCR + WB)
	[31]				X	X	X	X
	[62]				X	X
	[79]	X
	[80]					X
	[81]					X
	[59]	X				X
	[82]					X
	[83]					X
	[84]					X			X	X							X
	[85]					X								X
	[86]				X	X								X
	[87]					X
	[66]					X
	[69]					X
	[88]	X				X							X
	[72]	X				X
	[89]			X	X		X
	[43]					X
	[40]					X								X
Rat	[90]					X								X			X
	[15]	X				X
	[91]	X				X
	[70]	X				X
	[92]	X				X
	[14]	X				X								X
	[93]	X				X
	[64]					X
	[45]	X				X	X
	[94]					X
	[95]	X	X
	[96]	X				X						X		X	X (AQP-4)
	[97]					X
	[98]	X		X		X
	[99]	X				X						X
	[27]					X	X					X	X	X	X (ELISA, PCR, WB)
	[100]	X				X						X	X	X	X (WB)
	[65]	X			X	X					X
	[101]	X				X
	[102]					X
	[32]	X				X	X
	[103]	X									X			X
	[58]	X
	[48]	X				X			X
	[49]	X				X
	[104]				X	X
	[26]	X				X									X (PCR)
	[105]	X				X									X (PCR)
	[106]	X										X		X	X (ELISA)
	[107]	X				X
	[108]	X				X
	[109]	X				X
	[71]	X				X
	[19]				X	X
	[110]				X									X
	[63]				X	X
	[33]					X	X					X			X (Plasma fibrinogen)		X
	[111]	X				X
	[112]	X				X
	[113]					X
	[114]					X
	[34]					X	X
	[115]					X
	[116]					X	X
	[117]	X									X		X
Rabbit	[20]	X				X
	[93]	X				X
	[28]					X	X	X
	[30]					X	X	X
	[118]					X
	[25]	X				X
	[119]					X
	[120]					X
	[121]					X
	[122]				X
Dog	[123]	X					X				X		X				X
Pig	[23]	X				X					X
Sheep	[29]			X	X	X		X				X
	[124]	X				X		X	X
NHP	[50]	X				X				X
	[21,22]	X														X (EMG)	X
	[44]	X
	[56]	X	X			X					X			X		X (EEG, SSEP)	X
	[125]	X
	[24]	X															X
	[126]	X				X	X		X	X							X
	[57]	X
	[127]	X
Human	[8]	X		X												X (EEG)	X
	[51]	X				X								X			X
	[54]	X												X			X
	[52]	X	X	X													X
	[9]	X															X
	[10]	X	X	X													X
	[11]	X															X
	[53]	X															X

PET: positron emission tomography; ΔT: thermometry; H/E: haematoxylin and eosin; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labelling; VF: vanadium acid fuchsin; LB: Luxol fast blue; CV: Cresyl violet; PB: Perl’s Prussian blue; Iba1: ionized calcium-binding adaptor molecule 1; GFAP: glial fibrillary acidic protein; PCR: polymerase chain reaction; WB: Western blotting; ELISA: enzyme-linked immunosorbent assay; EMG: electromyogram; EEG: electroencephalography; SSEP: somatosensory evoked potentials