The Effect of Electromagnetic Field Treatment on Recovery from Ischemic Stroke in a Rat Stroke Model: Clinical, Imaging, and Pathological Findings

Abstract

Stroke is a leading cause of death and disability. Effects of stroke include significant deficits in sensory-motor skills and cognitive abilities. At present, there are limited effective interventions for postacute stroke patients. In this preliminary research we studied a new noninvasive, very low intensity, low frequency, electromagnetic field treatment (VLIFE), targeting a neural network, on an in vivo stroke rat model. Eighteen rats were divided into three groups: sham (M1) and two treatment groups which were exposed to VLIFE treatment for 4 weeks, one using theta waves (M2) and another using beta waves (M3); all groups were followed up for an additional month. Results indicate that the M2 and M3 treated groups showed recovery of sensorimotor functional deficits, as demonstrated by Modified Neurological Severity Score and forelimb placement tests. Brain MRI imaging results show a decrease in perilesional edema and lateral ventricle widening in the treated groups. Fiber tracts' imaging, following VLIFE treatment, showed a higher white matter integrity compared to control. Histological findings support neural regeneration processes. Our data suggest that VLIFE treatment, targeting a specific functional neural network by frequency rather than location, promotes neuronal plasticity after stroke and, as a result, improves clinical recovery. Further studies will investigate the full potential of the treatment.

Figure 1

Figure 2

Modified Neurological Severity Scale. Modified Neurological Severity Score was tested in 15 animals at days 1, 11, 19, 27, 35, 43, and 57. M1 group received sham treatment, M2 was exposed to 3.93 Hz, and M3 was exposed to 15.72 Hz VLIFE 2 min sessions, in alternate days, for a month and followed up for an additional month. Values are mean ± SE of the difference from day 1; p = 0.002 for M2 and p = 0.02 for M3.

Figure 3

Forelimb placement test. Forelimb placement, reflecting sensorimotor deficit recovery, was tested in 15 animals at days 1, 11, 19, 27, 35, 43, and 57. M1 is a group receiving sham treatment, M2 was exposed to 3.93 Hz and M3 was exposed to 15.72 Hz VLIFE 2 min sessions, in alternate days, for a month and followed up for an additional month. Values are Mean ± SE of FPT difference from day 1. p = 0.036 for M2 and p = 0.04 for M3.

Figure 4

Edema and right ventricle's volume (affected hemisphere). The edema region was measured in each time point in the T2 maps, the region of high intensity T2 was measured in all slices (a). Quantitative data of edema's volume (b) and right ventricle's volume (c) is shown in each rat at each time point in one representative MRI slice. One day after tMCAO (TP1), two weeks after the first treatment (TP2), 1 month after the first treatment (TP3), one month after the final treatment session (TP4). M1 is a group receiving sham treatment, M2 was exposed to 3.93 Hz, and M3 was exposed to 15.72 Hz VLIFE 2 min sessions, in alternate days, for a month and followed up for an additional month.

Figure 5

Measured T2 and ADC of the affected and unaffected hemispheres. A quantitative evaluation from MRI T2 sequence ((a), (b)) and ADC (Apparent Diffusion Coefficient) sequence ((c), (d)) maps of each rat during the different time points. The right (affected) and left (unaffected) hemispheres were compared at different time points as described in Figure 4 (TP1–TP4) in untreated animal group (M1) and treated groups as described in Figure 4 (M2, M3).

Figure 6

DTI of corpus callosum. A reconstruction of the corpus callosum white matter system (a) of the 3 examined rat groups (M1, M2, and M3 as described in Figure 4) at 3 time points (TP1, TP2, and TP4 as described in Figure 4). The median diffusivity of the fiber system was extracted and is shown in (b).

Figure 7

DTI of fornix-fimbria. A reconstruction of the fornix-fimbria white matter system (a) of the 3 examined rat groups (M1, M2, and M3 as described in Figure 4) at 3 time points (TP1, TP2, and TP4 as described in Figure 4). The median diffusivity of the fiber system was extracted and is shown in (b).

Figure 8

DTI of internal capsule. A reconstruction of the internal capsule white matter system (a) of the 3 examined rat groups (M1, M2, and M3 as described in Figure 4) at 3 time points (TP1, TP2, and TP4 as described in Figure 4). The median diffusivity of the fiber system was extracted and is shown in (b).