Saxena T; Khichi G; Saxena M

Research Article

Austin J Cerebrovasc Dis & Stroke. 2017; 4(2): 1059.

Cell Death in Stroke: Role of Metabolism

Saxena T¹*, Khichi G² and Saxena M³

¹Department of Internal Medicine, Mittal Hospital and Research Centre, India

²Department of Radio Diagnosis, Mittal Hospital and Research Centre, India

³Department Yoga and Physical Education, Mittal Hospital and Research Centre, India

*Corresponding author: Tarun Saxena, Department of Internal Medicine, Mittal Hospital and Research Centre, India

Received: April 19, 2017; Accepted: May 15, 2017; Published: May 29, 2017

Abstract

>Background: Stroke is one of the major causes of mortality and morbidity. Un-availability of oxygen due to acute reduction in blood flow is the prime reason for stroke. Despite extensive work-up 40% cases of stroke remain unexplained. The role of metabolism in stroke remains unidentified. Could metabolism play a role in cellular death in stroke? This was the main focus of the study.

Methods: This is a descriptive study done retrospectively, through data collection in intensive care and emergency unit of Mittal Hospital Ajmer, India. Arbitrarily record of 200 cases admitted between July 2016 and January 2017 was observed. The data examined was clinical profile, vital parameters, Echocardiography, Magnetic resonance imaging (MRI) and MRI angiography, Carotid Doppler study and Sympathetic skin response (SSR).

Results: MRI suggestive of infarct, maximum in MCA (middle cerebral artery) territory 50% cases had abnormal MRI angiography, 40% had abnormal Carotid Doppler study.

Conclusions: In almost a 40-50% of cases no obstruction in cerebral blood flow/oxygen supply was found. After entering into cells oxygen takes part in aerobic respiration to generate ATP (Adenosine tri phosphate). Therefore it is presumed that in the presence of normal oxygen supply some defect in ATP generation at cellular level is present. This may occur when there is a sudden change in demand of ATP secondary to sudden change in BMR, and cells are unable to generate ATP at a new speed, leading to cell death.

Keywords: Stroke; Cell death; Metabolism; Aerobic respiration; Adenosine tri phosphate (ATP)

Introduction

Worldwide, the incidences of stroke are on a rise [1-4]. Prevention of cell death remains important in stroke. Reduction in blood flow due to critical narrowing (atherosclerosis) or acute thrombo-embolic occlusion leads to unavailability of oxygen and produces cell death in brain [5-7]. This is the primary reason; however, despite complete evaluation reasons for cell death are not understood in 30-40 percent of cases [8]. Similarly, it is unclear how atherosclerotic narrowing developed over years becomes critical in a few minutes. Is there a sudden increase in oxygen or ATP (Adenosine tri phosphate) demand? Are there other factors that affect cell death? The role of metabolism in cell death in stroke remains unclear. A few studies have suggested inhibition of oxidative metabolism [9-10] that leads to cell death. Still, a clear relationship between metabolism and stroke is yet not decided. Therefore, this study was planned to find any correlation between metabolism and stroke.

Methods

This is a descriptive study done in a retrospective manner based on data collection through Emergency department and Intensive care unit of Mittal hospital and research centre, Pushkar road Ajmer. The hospital is in Ajmer (a city situated in the central part of Rajasthan, India). Arbitrarily record of 200 cases admitted between July 2016 and January 2017 was observed. The following parameters were examined

Clinical profile at 0 hour (admission time) and 48 hours
Past history of hypertension/diabetes/stroke/cardiac event
Vital parameters including pulse rate, blood pressure, temperature, oxygen saturation (Spo2) at the time of admission
Blood investigations including sodium, potassium, calcium, blood glucose, urea, creatinine, Lipid profile
Electrocardiogram, Echocardiography
Magnetic resonance imaging (MRI), MRI angiography/Carotid Doppler study
Sympathetic Skin response (SSR)

Results

ACA - anterior cerebral artery

MCA- middle cerebral artery

PCA –posterior cerebral artery

Abnormal MRI angiography- Reduced or absent flow due to presence of thrombus/hypoplasia.

Abnormal Carotid Doppler- significant (>70%) narrowing/ presence of unstable plaque.

TIA- Transient ischemic attack

50% of cases of acute stroke had abnormal MRI angiography. 40% cases had abnormal Carotid Doppler study.

Discussion

Worldwide, the incidences of stroke are on a rise. Reduction in blood flow produces infarction/ischemia/penumbra zone depending upon severity of unavailability of oxygen in 50% -55% of cases. Despite extensive evaluation etio-pathogenesis of 30%-40% of cases of stroke remains unexplained [8]. Preservation of cell tissue in stroke remains important. The role of metabolism in cell death in stroke remains dubious. A few studies have depicted the role of inhibition of oxidative metabolism in cell death. Still a clear relationship between metabolism and stroke is not documented. Therefore, this study was planned to observe any correlation between metabolism and stroke.

The study was done in a descriptive, retrospective manner through data collection in Mittal Hospital and Research Centre, Pushkar road Ajmer, Rajasthan, India. Hospital record of 200 cases admitted between July 2016 and January 2017 were observed.

The age group of cases was 50 -75 years. 65 percent were males and 35 percent were females (Table 1).

Table 1: General examination.




  
    Mean 
      Age 
    Sex 
    Mean pulse rate/minute 
    Mean blood pressure mm Hg (0 hour) 
    Mean blood pressure mm Hg (last 12 months) 
    Smoker 
    Diabetes 
    Dyslipidemia 
    Spo2 (oxygen saturation) 
    History of TIA 
  
  
    50-75 years
    65 % male
      35% Female
    80±4
    160/90 in 40%
    156/90 in 40%
    15%
    55%
    30%
    96-99%
    7%



Table 1: General examination.

Initially, we look at the findings of three different cases. In case 1 (Figure 1) there is normal left vertebral, basilar and normal bilateral posterior cerebral arteries, right vertebral is hypoplastic. There is left occipital lobe infarct. In case 2 (Figure 2), there is large right middle cerebral artery (MCA) infarct despite, normal Carotid Doppler study and normal MRI angiography including right MCA. In case 3(Figure 3) there is critical narrowing in cervical part of left internal Carotid artery (ICA), patient coming for routine check- up, clinically normal . Therefore, there is a mismatch, i.e. one to one relationship (i.e. compromise- infarct) is not present.

Figure 1: MRI angiography, MRI Flair and MRI diffusion image.

    
    
    Figure 1:  MRI angiography, MRI Flair and MRI diffusion image.

Figure 2: Special investigations.

    
    
    Figure 2:  Special investigations.

Figure 3: Color Doppler left ICA –axial view (76% narrowing).

    
    
    Figure 3:  Color Doppler left ICA –axial view (76% narrowing).

What does the investigation suggest-?

MRI- Infarct (100%) - ACA (15%), MCA (50%), PCA (10%), Vertebro–basilar (25%)

MRI angiography- Normal (50%), Abnormal (50%)

Carotid Doppler (critical narrowing) - Normal (60%), Abnormal (40%)

Echocardiography- Thrombus in 2% only (Table 2)

Table 2: Special investigations.




  
    MRI Brain(infarct) 
    MRI Angiography 
    Carotid Doppler 
    Carotid 
      Doppler(intima media thickness >0.9 mm 
    Electro- Cardiography 
    Echo- Cardiography 
    Sympathetic Skin response 
  
  
    15% ACA
    Abnormal 50%
    Abnormal
      40%
    20%
    Rhythm disturbance- none
    RWMA 10%
    Huge spikes 85%
  
  
    50% MCA
    Normal 50%
    Normal 60%
     
     
    Thrombus 2%
     
  
  
    10% PCA
     
       
     
     
     
     
     
  
  
    25% Vertebro-basilar



Table 2: Special investigations.

Atherosclerosis risk factors - Hypertension (40%), Diabetes (55%), dyslipidemia (30%), Carotid intima media thickness >0.9 mm (20%), smoking (15%) Presence of hypertension was there in 40 % of cases (mean blood pressure 160/90 mm Hg) but these cases were previously hypertensive (156/90 mm Hg mean blood pressure during last one year). The difference was not significant during the last one year and at the time of the stroke. Long standing blood pressure is a risk factor atherosclerosis but precipitating acute stroke without significant rise from previous mean value remains uncertain (Table 2) [11-14].

Sympathetic activity - Resting pulse rate was within normal limits, so there was no overt increase in sympathetic activity (Table 1). High base line sympathetic activity (80% SSR Spikes) (Figure 4) was present. Directly increased sympathetic activity preserves circulation and oxygen supply to vital organs including brain [15-17], therefore direct effect of increased sympathetic activity can’t precipitate stroke. On the contrary increased sympathetic activity increases oxygen demand of the tissues [18].

Figure 4: Sympathetic skin response.

    
    
    Figure 4:  Sympathetic skin response.

After going through investigations, it was found that there is a mismatch i.e. infarct 100% and abnormal flow maximum up to 50%. Even a normal person coming for routine check- up has 75% (critical) narrowing in ICA. The similar degree of critical blockage becomes significant, in the same person or another person when it produces injury to brain?

Critical narrowing (> 70%) is mainly atherosclerotic reduces blood and oxygen flow to brain. Atherosclerosis is a chronic process; chronicity always gives a chance to body to adapt to reduce blood flow. Absence of chronic symptoms/preceding TIA (transient ischemic attack) in the maximum number of cases (preceding TIA only 7%) (Table 1) ; and acute appearance of stroke gives rise to the question of precipitating factor in the same narrowed vessel i.e. in the same vessel diameter one day the person is normal and develops stroke another day. How does the critical narrowing become even more critical?

There is no clear answer to such questions as to why stroke occurred in 50% nearly normal or normal cerebral circulation. It seems that in 40 %-50% of cases despite sufficient blood flow and oxygen supply cell injury occurred. We have to trace the role of oxygen after reaching to the cell. Oxygen takes part in aerobic respiration/ cellular metabolism and generation of ATP. Therefore, the possible mechanism may be there in cellular metabolism.

For normal cell functioning in brain, cells require glucose and oxygen and oxygen utilizing activity of cell i.e. activity sufficient to generate ATP through aerobic respiration or cellular metabolism. Cellular metabolism includes glycolysis, oxidative decarboxylation, citric acid cycle and oxidative phosphorylation to produce ATP (Adenosine tri phosphate) [19,20] (Figure 5). Rate of cellular metabolism/ATP generation is in turn decided by basal metabolic rate (BMR) [14]. BMR is decided by hypothalamus according to external environmental temperature [21]. BMR is the minimum cell activity to produce ATP required for it’s survival in a particular season.

MRI Brain(infarct)	MRI Angiography	Carotid Doppler	Carotid Doppler(intima media thickness >0.9 mm	Electro- Cardiography	Echo- Cardiography	Sympathetic Skin response
15% ACA	Abnormal 50%	Abnormal 40%	20%	Rhythm disturbance- none	RWMA 10%	Huge spikes 85%
50% MCA	Normal 50%	Normal 60%			Thrombus 2%
10% PCA
25% Vertebro-basilar

Cell Death in Stroke: Role of Metabolism

Abstract

Introduction

Methods

Results

Discussion

Possible Clinical Implications

Acknowledgement

References