Intrinsic Mechanisms of Acupuncture in Ischemic Stroke Rehabilitation

Author: Livia Popa

Keywords: acupuncture in ischemic stroke rehabilitation; cerebral ischemia; basic research; stroke; rehabilitation

Ischemic Stroke – Pathophysiology, Treatment, Associated Impairments, and Rehabilitation

Currently, the second-leading cause of death worldwide, stroke is an acute injury of the central nervous system, and a vascular cause triggers it. There are two major categories of stroke: hemorrhagic (~20% of strokes) and ischemic (~80%) (Figure 1). 

Figure 1. Stroke categories

In almost 90% of acute strokes, a compromised vascular supply to the brain is the primary event; ischemia’s duration, severity, and location determine the damage extent [1]. 

Once cerebral ischemia occurs, the main focus in the treatment protocol is the prevention or the reversal of brain injury, together with the optimization of cerebral perfusion, by dilating the blood vessels [2].

Loss or alteration of sensory-motor skills are the most common impairments following stroke [3], and the rehabilitation solutions include the following, in addition to medication:

• early physical, occupational, and speech therapy,
• cognitive rehabilitation, 
• exercise programs,
• bilateral arm training (e.g., mirror therapy),
• walking aids,
• neuromuscular electrical stimulation. 

All these practices have the sole purpose of assisting with the patient’s accelerated recovery and reintegration into daily life activities [2]. Acupuncture can also be considered among rehabilitation therapies [3].

What are the intrinsic mechanisms of acupuncture in ischemic Stroke Rehabilitation?

Acupuncture, a procedure that consists of inserting a fine needle into the skin or deeper tissues in the acupoints (specific locations of the body), either manually, electrically, or by using heat, is one of the oldest, famous and studied practices in Chinese medicine [4, 5]. In recent studies, acupoints have been suggested to be excitable skin-nerve/muscle complexes with a very high density of nerve endings. Practicing manual acupuncture or electroacupuncture at certain acupoints has been shown to stimulate afferent fibers, sending signals to the spinal cord [6]. Enhanced balance, reduced spasticity, and an increase in muscle strength have been identified as acupuncture benefits in clinical trials [7] (Figure 2). 

Figure 2. Clinical benefits of acupuncture

The reviews and meta-analysis of randomized trials conducted in 2010 suggested acupuncture as an effective practice that generates improvements in post-stroke impairment treatment due to its analgesic effect in motor rehabilitation, promoting increased perfusion within peri-infarcts and low perfusion zones and stimulating neuronal reorganization [8]. However, the exact mechanisms behind its alleviating effects must be determined for acupuncture to be implemented as a clinical practice.

Although there are limitations to this kind of literature review (such as experimental conditions in which stroke is induced that are not identical to the clinical environment, anesthesia used during the experimental practice of acupuncture on animals, without a clear understanding of how the mechanisms of acupuncture are affected by anesthesia), it has been stated that in general, the inclusion of acupuncture in the acute stages of stroke recovery practices reduces infarct volume and neurological deficits.

Review of literature – purpose, methods, results

As the exact processes behind the positive effects of acupuncture in stroke rehabilitation are unclear, one recent literature review focused on the available information regarding the mechanisms behind the effectiveness of acupuncture for rehabilitation in ischemic stroke, reduction of post-stroke infarct volume, and neurological deficits [5].

Chavez et al. [5] reviewed some PubMed full-text studies published in English from the 1st of January 2000 to the 31st of December 2015, filtered by three key notions: Acupuncture, Cerebral Ischemia, and Effect; 105 articles resulted from this basic search. Further filtering of the results was done considering some relevant inclusion criteria: specific mechanisms that describe how acupuncture exerts its effects, ischemic stroke type, acupuncture exclusively used after ischemic injury, and the related studies indicated in the resulting articles.

This resulted in a total of 40 articles representing the source of the current review. These studies have in common a similar model in animal experiments performed on several species of mice, which presented permanent or temporary occlusion of cerebral arteries, internal, external, or common carotid arteries. Also, in all the studies, acupuncture or electroacupuncture was part of the post-surgery protocol [5].

The review of these articles resulted in the identification of five main mechanisms on which the effects of acupuncture in stroke rehabilitation rely. Each of the five mechanisms, further detailed, is represented in Figure 3.

Figure 3. Acupuncture mechanisms in stroke rehabilitation [6].

1. Promotion in neurogenesis and cell proliferation in the Central Nervous System (CNS) 

The ischemic stroke affects the CNS-resident cells to such a degree that the development of two significant zones takes place, depending on the degree and the duration of ischemia: the ischemic core (where cell death is immediate) and the ischemic penumbra (where the initial damage alters the function of the tissue, even when its structure is intact). Due to the reversibility of damage in the ischemic penumbra, acute stroke therapy targets this zone particularly [9]. 

Cell proliferation in the CNS after ischemic stroke is promoted by acupuncture through two different mechanisms:

• Neurogenesis – acupuncture leads to an improvement in the division of stem cells; 
• Proliferation – promoted by acupuncture in ischemic-affected tissue and some contiguous zones to the damage caused by the middle cerebral artery occlusion [5].

2. Regulation of Cerebral Blood Flow

During an ischemic event, the direct injury or cell death, the alteration of the blood-brain barrier, and the microvascular injury result in the loss of vascular structural integrity [1]. Ischemia triggers a natural neuroprotective mechanism – active angiogenesis – the formation of new blood vessels starting within twelve to twenty-four hours after a stroke and can go on for a minimum of twenty-one days afterward [1]. It is also worth mentioning that, during ischemia, reduction in the infarct lesion and associated secondary damage can be ensured by vasodilative mediators used in the acute stages.

Acupuncture has been linked to two different types of activities that involve the regulation of blood flow in the cerebral cortex:

• An enhancement in the expression of the angiogenic factors promoted by electroacupuncture, complemented by inhibition in the antiangiogenic factors production [5];
• A vasoactive modulation is an electroacupuncture effect of increased perfusion on the affected area (increased cerebral blood flow) and vasodilation [5].

1. Anti-Apoptosis

After a stroke, the neuronal populations go through a cell death-regulated process, with minimal inflammatory reaction or genetic material release, called apoptosis [8], one of the most common mechanisms on which most studies related to stroke rehabilitation focus. If the apoptosis is inhibited, the ischemic injury can be reduced, and activation of cell death is prevented [10].

Manual acupuncture has been shown to suppress pro-apoptotic factors and to upregulate the expression of a protective protein that regulates cell death [5]. In contrast, electroacupuncture has shown effects in the enhancement of the levels of anti-apoptotic factors, together with the inhibition of apoptotic mediators [5].

2. Regulation of Neurochemicals

Various complex processes are involved in ischemic stroke – lack of oxygen and glucose results in an energy failure that further leads to cell injury and cell death, as a result of several interdependent molecular pathways, like excitotoxicity, oxidative stress, nitrative stress, inflammation, apoptosis [11].

Stimulation of certain acupoints can increase the level of dopamine and modulate neuronal plasticity, reducing the degree of cerebral atrophy post-ischemia [5]. Electroacupuncture applied on several acupoints has been shown to prevent neuronal apoptosis [12], increasing the percentage of surviving neurons in the cerebral cortex and reducing infarct volume [5].

Also, as cerebral metabolic activity depends on the constant supply of oxygen and glucose provided by normal circulation, it is especially vulnerable to interruptions in the regular blood flow and, consequently, oxidative stress [13]. Furthermore, it has been noted that stimulation of several specific acupoints increases the activity of antioxidant enzymes, so acupuncture has antioxidative effects [14], thus promoting neurological recovery. According to studies included in the review, electroacupuncture is also effective in reducing inflammation and improving functional and motor recovery.

3. Modulation of Long-Term Potentiation and Memory Improvement

Long-term potentiation (LTP) represents an increase of synaptic strength in the hippocampus (the cerebral structure located in the temporal lobe, playing a vital role in memory and learning processes), after intense stimulation. Following an ischemic stroke, the hippocampal subfield becomes unpaired, and this cellular model of learning and memory formation by synaptic transmission is affected. Acupuncture has been observed to help facilitate these processes through the modulation of different pathways [5]. Manual acupuncture at specific acupoints has improved cognitive hippocampus function and reduced LTP-related deficits caused by excitotoxicity.

Conclusions | Acupuncture in Ischemic Stroke Rehabilitation

As the world around us is changing every day, so are medical practices; new approaches in post-stroke recovery emerge on a regular basis, offering support and hope to both medical personnel and patients. Along with other alternative practices, like robotic-assisted therapy, and mirror therapy, acupuncture is more and more linked to improvements in post-stroke recovery.

In several animal studies, acupuncture benefits in ischemic stroke rehabilitation have been observed through five major mechanisms, as shown in Figure 4.

Figure 4. Acupuncture benefits in ischemic stroke

Overall, the inclusion of acupuncture during the acute stages of stroke recovery has been shown to reduce infarct volume and neurological deficits as well.

Studies revealed that acupuncture helped alleviate neurological deficits and reduced brain edema in ischemic stroke [5]. Also, acupuncture improved global deficiency and some specific neurological impairments without serious adverse effects [5].

Furthermore, while they are a topic for further study and discussion, the identified benefits of acupuncture are encouraging and give hope to millions of patients confronting dramatic stroke-related damage.

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