Table 7 Summarizing the data of all preclinical studies in TBI specifying the design, objectives, methodology, results, and conclusion

66

Animal study (rat spinal cord injury model)

Investigate the effects of 25-Hz rTMS

on glial activation in a spinal cord

injury-induced pain model

25-Hz rTMS applied for eight weeks to lamina II and III

and spinal dorsal horn. Assessed numbers of microglia

(Iba1) and astrocytes (GFAP) at the L4-L5 level

Significant reduction in Iba1 + microglia and

GFAP + astrocytes in the dorsal and ventral

horns of the spinal cord

25-Hz rTMS reduces glial activation, offering potential

therapeutic benefits in spinal cord injury-induced pain

67

Animal study (mouse skulls with HIFU)

Examine the effects of 1.5 MHz

high-intensity focused ultrasound (HIFU)

pulse trains on astrocytes and microglia activation

Applied HIFU to mouse skulls. Measured GFAP density

and microglial marker ionized calcium-binding adaptor

molecule in the cortex, corpus callosum, and hippocampus

Increased GFAP density and microglial marker,

along with astrocyte reactivity

HIFU induces glial activation and can be used to study

biological effects of non-impact mild traumatic brain injuries

68

Animal study (sterile inflammatory response model)

Investigate the effects of pFUS + MB

on sterile inflammatory response (SIR)

and associated pathways

pFUS + MB treatment analyzed for DAMP response, heat-shock

protein 70, IL-1, IL-18, TNFα, neurotrophic/neurogenesis factors,

NFκB pathway activation, macrophage infiltration, and vascular

cell adhesion molecule expression

Induced DAMP response with elevated pro- and

anti-inflammatory factors, NFκB pathway activation,

macrophage infiltration, and transient SIR similar

to ischemia or mild traumatic brain injury

pFUS + MB triggers SIR resembling ischemia or mild TBI,

with potential therapeutic and research applications

69

Systematic review (820 PTBICD patients)

Assess the efficacy of rTMS combined

with cognitive training (CT) on cognitive

and functional outcomes in post-traumatic

brain injury cognitive disorder (PTBICD)

Reviewed 820 patients across multiple studies. Evaluated cognitive

function, mental state, daily activities, and P300 latency/amplitude

as biomarkers

rTMS combined with CT significantly improved cognitive

function, mental state, daily activities, and correlated

with P300 biomarker modulation

rTMS combined with cognitive training enhances recovery

in PTBICD patients, improving functional and cognitive outcomes

70

Therapeutic innovation review

Explore the mechanisms and therapeutic

potential of transcranial photobiomodulation (PBM)

using red to near-infrared light for brain function modulation

Reviewed PBM parameters (wavelength, power density, dose,

positioning, pulse frequency) and their effects on neuronal

microstructures like microtubules and tubulins

PBM influences electrical properties and polymerization

dynamics of neuronal microstructures, with outcomes

modifiable by specific parameters

PBM represents a novel therapeutic approach for modulating

brain functions through precise parameter adjustments