Clinical Report on the Treatment of Post-stroke Cognitive Impairment Based on Microbe-Gut-Brain Axis Theory

Zhonghui ZENG, Lingyun ZHOU, Zeyu ZHANG

1. Guizhou University of Traditional Chinese Medicine, Guiyang 550002, China; 2. Cadre Health Care Department, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550003, China

Abstract Based on the close relationship between MGBA and PSCI, one PSCI related case is reported, and it is emphasized to improve clinicians’ understanding of MGBA theory in the treatment of PSCI, thereby providing new ideas for exploring pathogenesis and treatment of PSCI.

Key words Microbe-gut-brain axis, Post-stroke cognitive impairment, Gut microbe

1 Introduction

Cognitive impairment is one of the senile syndromes[1], and it could affect patients’ attention ability, spatial ability, language and executive ability[2]. A complex signal network system constituted by human intestinal microorganisms, intestinal nervous system, autonomic nervous (MGBA) system and central nervous system is MGBA (MGBA)[3], while probiotics may be one of the effective means to prevent or improve cognitive decline[4-5]. This paper reports a related case, and it is emphasized to improve clinicians’ understanding of MGBA theory in the treatment of PSCI (PSCI), to provide diagnosis and treatment experience.

2 MGBA and PSCI

MGBA is a theory proposed in recent years to explain the relationship between brain and intestinal microorganisms[6]. The gut contains millions of microorganisms, which can play an important role in the gut-brain axis and have a significant impact on human health[7]. Intestinal flora is widely involved in the synthesis and release of active compounds such as hormones, active metabolites and neurotransmitters, which affect brain function and host behavior[8]. On the one hand, studies suggest that intestinal microorganisms can affect brain function by stimulating vagus[9]to introduce signals to the brain, activating hippocampal nerves[10]and microglia, resulting in brain neuron dysfunction and cell necrosis[11]. On the other hand, it can destroy the blood-brain barrier through immune system[12]and inflammatory factors to produce pro-inflammatory effect and disturb the homeostasis of brain nervous system[13]. Moreover, intestinal microorganisms activate the maturation of microglia by their metabolites (short-chain fat emulsion, amino acids, peptides,etc.)[14]passing through the blood-brain barrier to damage the central nervous system and cause its immune imbalance[15]. MGBA is bidirectional[16], and the central nervous system can regulate the intestinal tract and intestinal nervous system through sympathetic and parasympathetic nerves, affect the permeability and barrier function of the intestinal tract, and then affect the intestinal microbial homeostasis[17]. PSCI refers to the decline of cognitive function after stroke, and it can be prevented and treated[18]. The changes of intestinal microorganisms can control the occurrence of inflammation in the central system and reduce β-amyloid deposition and Tau protein hyperphosphorylation in the brain, further improving cognitive dysfunction and slowing down the development of cognitive decline[19]. Similarly, post-stroke stress response stimulates the hypothalamus-pituitary-adrenal axis hormone regulation disorder, which also accelerates the intestinal permeability, resulting in the enteric bacterial translocation and causing decrease of intestinal flora diversity. Therefore, there is a complex mechanism between MGBA and PSCI, and there are few clinical reports that regulating intestinal flora based on MGBA theory can improve the prognosis of PSCI.

3 Typical case

The patient is an elderly, male, 90 years old, with a history of cerebral infarction for 7+years, and his memory decreased 5+years ago. The main manifestations are recent memory loss, and his computational ability, understanding ability, time, spatial orientation and executive ability decrease. Physical examination: nervous system examination: clear mind, pertinent answers, astringent speech, normal function of senior cortex, symmetrical forehead lines on both sides, equal size and equal circle of pupils on both sides, sensitive reflection to light, flexible eye movement, shallow nasolabial groove on the left compared with the right, oblique angle of mouth to the right and left deviation of tongue extension; the uvula is left, and the pharyngeal reflex is dull, and the other cranial nerves are negative; the muscle strength of the left limb is Grade 2, the muscle strength of the right limb is Grade 5-, the muscle tension of the left limb is increased, the muscle tension of the right limb is normal, the tendon reflex of the left upper limb (+++), the Babinski sign, Gordon sign, Chaddock sign and Pussep sign on the left (+), and the remaining pathological signs are not drawn out. The pain and temperature sensation of the left limb is lower than that of the right, and the meningeal stimulation sign is (-). Auxiliary investigation: head CT: multiple lacunar cerebral infarction in the right basal ganglia and apical lobe. Relevant evaluation: mini-mental status examination (MMSE): 10 scores.

In conclusion, combined with clinical manifestations, past history, imaging examination and relevant evaluation, he is diagnosed as PSCI. Clostridium Butyricum Enterococcus Triple Viable Tablets are given to regulate intestinal flora, and Rabeprazole Sodium Enteric Coated Tablets are given to inhibit acid and protect the stomach, while Mosapride Tablets are given to promote gastrointestinal motility. After years of follow-up after treatment by regulating intestinal flora, it is found that the patient’s memory is improved, and now he can simply calculate, and MMSE is 12 scores. It can be seen that the patient’s relevant cognitive performance and score have been improved compared with before, and the cognitive impairment has not been further aggravated after treatment.

4 Discussion

PSCI refers to the symptoms and cognitive impairment of different severity after the occurrence of cerebrovascular disease, belonging to one of geriatric syndromes[20]. Its clinical manifestations often include memory disorder, learning ability disorder, attention disorder, sensory and perceptual disorder, executive disorder, affective disorder, personality change and abnormal behavior[21]. The cognitive assessment of patients can be carried out by means of scale measurement, function test and screening method, and it can be repaired by drugs, exercise, occupational therapy, traditional rehabilitation and other treatments[22-23]. The diagnostic criteria of PSCI proposed by Vascular Cognitive Impairment Branch of Chinese Stroke Association in 2021 include clinical, imaging and neuropsychological evaluation[24]. Therefore, clinical evaluation is an inevitable condition in the diagnosis of PSCI[18].

Characteristics of this case: (i) recently, the patient suffered from memory loss, decreased calculation ability, understanding ability, time, space orientation, and execution ability, and choked with drinking water, MMSE: 9 scores. (ii) The patient had a history of cerebral infarction for more than 7 years, and now had symptoms of limb weakness, walking drag and speech jerkiness, and head CT showed multiple lacunar cerebral infarction in the right basal ganglia and frontal parietal lobe. (iii) The memory has been improved after oral probiotic treatment, and simple calculation can now be carried out, MMSE: 12 scores. (iv) The patient has been hospitalized for a long time. After probiotics were given to regulate intestinal flora and improve cognitive function, the symptoms and scores have not been further aggravated since many years of follow-up.

In terms of treatment, PSCI treatment includes drugs[23]exercise, occupational therapy, rehabilitation,etc[25]. Among them, common drug treatment includes calcium antagonists, excitatory amino acid receptor antagonists and cholinesterase inhibitors[26]. After the brain-gut-microbiota axis theory was put forward, great attention has been paid to the relationship between intestinal microorganisms and PSCI[27]. The mechanism may be that the intestinal microbiota synthesize various neurotransmitters and neuromodulators, such as serotonin, dopamine, γ-aminobutyric acid and short-chain fatty acids to affect the function of the central nervous system[28]. The study by Singhetal.[29-30]showed that there is a two-way relationship between intestinal flora and brain. After PSCI, it can cause intestinal flora disorder. At the same time, abnormal intestinal flora can also affect the prognosis of PSCI through immune-mediated[31]. After some intestinal strains produce neurotransmitters such as γ-aminobutyric acid, serotonin, dopamine and adrenaline, they are transmitted to the brain through the intestinal nervous system, which can have a positive or negative impact on cognitive function, mediate signal pathway of inflammatory factor and regulate nervous system function[32-33], especially the probiotics. For example, γ-aminobutyric acid produced byLactobacillusandBifidobacteriumregulates cognitive function by acting on brain activities through G-protein coupled receptors[34]. It can be seen that supplementing probiotics has become a new method to intervene PSCI in recent years.

The literature shows that probiotic supplementation can improve cognitive function, metabolic state and intestinal microbial disorder in patients with PSCI[35-36]. By increasing cholinergic neurotransmitters in hippocampus and cerebral cortex, it could reduce neurodegenerative changes in eyes, prevent memory loss induced by amyloid accumulation[37]. The supplementation of probiotics could increase regulatory T cells and reduce interleukin-17 positive T cells, thereby inhibiting transport of effector T cells from intestine to center after stroke. It illustrates the effect of probiotics on PSCI from the aspects of immune and inflammatory mechanisms[38-39]. Probiotics can also interfere with the microbial ecology of gastrointestinal tract and improve the progress of PSCI, which also suggests the potential of applying microbiota and its corresponding metabolites to the early clinical diagnosis and treatment of PSCI[40]. Moreover, studies have shown that probiotics can enhance the anti dementia activity of memantine and curcumin[41]. So, taking probiotics has a positive therapeutic effect on PSCI.

5 Conclusions

In summary, there is a close relationship between microbe-gut-brain axis and PSCI. Malfunction of microbe-gut-brain axis mediated by intestinal microorganisms may play an important role in pathogenesis of PSCI. The mechanism between them is complex, and there is a two-way nature, which provides new ideas for exploring pathogenesis and treatment of PSCI. For the elderly, PSCI is one of geriatric syndromes, which has brought a heavy burden to the aging society. It should emphasize the assessment on PSCI, and then early prevention and treatment can be carried out. Therefore, it is worthy of further research and exploration in medicine in the future to pay attention MGBA to the complex relationship between PSCI and MGBA.