Sample Paper on Effects of Cocaine on Blood-Brain Barrier (BBB)

Effects of Cocaine on Blood-Brain Barrier (BBB)

Drugs have significant levels of effects on the lives of those using them. Different drugs have different effects on the people that use them. Cocaine’s effects on the brain have not been well understood by the scientific community. However, the effects appear significant to the human brain given that abuse of cocaine is often linked with vasculitis. Such conditions suggest an enhancement in conditions such as leukocyte mobility across the endothelial barriers (Acharya, Kaplan and Macdonald et al. 2487). Even though Cocaine’s effects in the body of the victims have not been well understood and documented, its abuse has been connected to various changes that take place in the brain imaging systems. These effects describe defects in the brain-blood barrier. Poor flow of blood and communication between the brain and various body organs results in poor communication and coordination of the body organs discussed. Different drugs affect the coordination of body organs thus affecting the entire body organs and structures.

The national survey of drugs Manco-Johnson, Abshire and Shapiro et al. (539) recognizes cocaine as one of the most abused drugs in the world. About 15 percent of Americans has used cocaine or cocaine contained drugs at least once in their lifetimes. One of the known effects of cocaine in the body of human beings is to alter the victims, behavior, as well as their moods. It has also been confirmed that cocaine causes euphoria in human beings. These effects have been associated with the mild effects of the drugs; however, other lethal and lasting effects have been associated with the consumption of cocaine. Among these, include a damaging effect on the persons’ judgments. Cocaine compromises the judgments capacity of the individuals that take them thus leading them to exhibit serious negative behaviors such as engaging in risky sexual behavior hence increasing the risks of contracting sexually transmitted infections such as HIV/AIDS.

Other than these effects, cocaine is suspected to have a myriad of additional effects in the lives of consumers. The side effects of these are far reaching and may impact greatly on the lives of these people. Besides, the fact that these drugs stay long in the brain of their consumers is an additional factor that makes it even more. Among the key effects, that cocaine has on the bodies of the persons that use the drug is causing brain barrier. This effect is dangerous and can lead to serious medical and neurological effects including the death of the victims. It is in light of these facts that this paper seeks to highlight the effects of cocaine consumption in causing brain barrier in the victims.

 Blood-brain barrier components

Before we go deep into cocaine intake affects blood-brain barrier, we will look at the Blood-brain barrier components in order to get the insights of how the consumption of cocaine can affect blood flow in the brains of the victims. Various reviews have described the components and structure of the BBB Dunn, Busch and Wyly et al. (422) and Wen, Jabbar, and Chen et al. (913). Hakobyan, Kazarian and Jabbar et al (2062) succinctly highlight that the brain-blood barrier is composed of certain highly specialized BECs that are in constant interaction with the pericytes, the vascular basement membrane as well as the astrocytes. The BECs, as Roosendaal, Vianen, and Wenting et al. (544) notes, are closely associated and connected to be in constant communication and interaction with one another from cell to cell inter-linkages. These cell to cell interlinks are made up of complexes of very tight junction molecules of protein, claudins, occludins as well as certain junctional adheisin molecules. Certain accessory protein components such as the zona occludins, cingulin and afadins are charged with the responsibility of providing support and stability to the tight and adherens junctions. On the other hand, the pericytes are concerned with the regulation of blood flow in the cerebral systems. They also stabilize the forming vessels such as veins and capillaries.

Neurovascular coupling at the blood-brain barrier interface

Having looked at the structural components of the BBB, we will look at the other aspect involving what happens at the BBB interface that makes it very crucial to the life of a person. A complex relationship often exists between the vascular and the neurological systems of the human body. Te interaction between the two components takes place within the CNS. The interactions between the two interfaces are often promoted by the BBB in conjunction with other elements such as the neurons, as well as the glia. Together, these components make up the neuro/gliovascular unit (Yao, Duan and Buch 243). The kind of neurovascular coupling results helps in the regulation of blood flow within the cerebral systems thus enabling the efficient and effective flow of oxygen as well as the supply of nutrients to the various brain cells (Toborek, Lee and Flora et al 191). Besides, theses, intercellular communication systems occurring within the neuro/gliovascular system allows for the localization of the control systems for blood flowing through the cerebral. This blood, flowing from the cerebral units is used to accomplish the various needs of the brain and is thus very useful to the normal functioning of the body of a human being. The interactions between the two systematic units, is, therefore very important in aiding the normal and continuous blood flow to the neurons and consequently, the rest parts of the body. Besides, blood flow within the neurons also aid in development and maintenance of the neurovasculature

Functions of the BBB

Having looked at the structural and properties of the BBB, we will look at the various functions of the system that makes it important in performing its functions in the brain. According to Kanmogne, Primeaux and Grammas (501), the functions of the various organs in the body of a human being us what makes it more important. All body organs are interconnected and enjoy some mutual relationships with one another. Negative effects on a single organ, therefore, results in either mild or acute effects on other related organs. The relationships that occur in the systematic communication between various organs forming the BBB make it very important to the whole body parts and organs. Owing to these interconnectivity and relationships in the functional activities of the various organs and systematic units making up the BBB, it is important that we look at the combined functions of the entire unit in order to delineate how cocaine intake affects each component and consequently the entire system.

The BBB system has several functions in the body of a human being. The main function of this unit, however, is the maintenance of the process of homeostasis during the process of blood circulation (Dhillon, Peng and Bokhari et al. 55). The introduction of various toxins into this system, therefore, is very dangerous and affects a wide range of things. Such toxins can be either endogenic or exogenic such as xenobiotics. Toxins result into impenetrability of the BBB. Physical inhibitions may also occur due to the presence of a tight junction connectivity that occurs on the BECs. Moreover, certain regulations on the transport of the associated organs can result in the limitation of the transcellular migrations (Virolle, Adamson and Baron 1125). Enzymatic activities taking place within the BECs is yet another inhibitory process that leads to the metabolism of the harmful substances at the vascular face of the BBB (Virolle, Adamson, and Baron et al. 1126). Another basic function of the BBB is to regulate the cerebral blood flow through the use of the pericytes. Also to these functional approaches, the cells found in the neuro/gliovascular tissues helps in secreting local vasoregulators such as norepinephrine, nitric oxides as well as the endothelin. These secretions regulate the cerebral blood flow (Virolle, Adamson, and Baron et al. 1127).

Under normal circumstances, the BBB functions to limit the entry of most of the leukocytes into the CNS. Increased immune cells migration through the BBB can result in the alteration of the structural components and organization at the tight junctions affecting its protein proteins as well as lead to the actin cytoskeleton remodeling within the BBB basement membrane. As Acharya, Kaplan and Macdonald et al. (2488) notes, the migrating peripheral immune cells often result into disruptions of the BBB functioning. Under such conditions, cytokines, such as tumor necrosis factor alpha interleukin as well as the CCL2 chemokine tend to increase the serum, neuronal tissues as well as within the cerebrospinal fluids existing within several components of the CNS. Such occurrences result in the occurrence of disorders related to the CNS such as traumatic brain injuries (Yao, Duan, and Buch), HIV-related encephalitis Roosendaal, Vianen and Wenting et al (544), as well as Huntington disease (Acharya, Kaplan and Macdonald  et al 2487).

Certain peripheral immune cells result in cases of increased production of inflammatory factors, neurotransmitters, neurotrophic as well as protease. These factors contribute immensely to neuroinflammation thus contributes to the continued alteration of the BBB. Through the application of neurovascular coupling, the BBB functions to regulate the cerebral blood flow. This is often accomplished through the action of the pericytes that are thought to regulate the vascular diameters as well as the cerebrovascular flows of blood.

How cocaine influences BBB

Considering the structural and functional benefits associated with the presence of the brain-blood barrier, how then the intake of cocaine influences this important balance. In this section, we shall look at the various ways and manners in which the brain-blood barrier interacts in the presence of cocaine. Various kinds of abused drugs result in pro-inflammatory effects in the neurological systems of humans. Some of the drugs that have been found to bear direct influence on such occurrences include stimulants such as cocaine. The occurrences of such pro-inflammatories lead to disruptions on the BBB (Dhillon, Peng and Bokhari et al. 55). Cocaine’s influences on the BBB are closely associated with the occurrence of the so said pro-inflammatories through a complex system of interactions and ordinations.

To begin with, the presence of cocaine in the blood of an individual inhibits the reuptake of monoamine especially through the binding DAT (Roosendaal, Vianen, and Wenting et al. 545). These effects were determined through a series of researches conducted in various laboratories. For instance, during the 1970 and 1980s when cocaine uptake was at its peak in the United States, it was discovered that the intake of cocaine-related drugs and substances led to the production of oxidative stress as well as neuroinflammation on various individuals tested for the drug. Some researches have linked cocaine abuse to terminal damages of the DA or even 5-HT (Dunn, Busch and Wyly et al. 415). This claim has been refuted in several writings that claim otherwise. However, cocaine use and abuse has been closely linked to the production of oxidative stress as well as neuroinflammation in the victims. Oxidative stress and neuroinflammation have very toxic consequences on the neurological systems of human beings. According to Roosendaal, Vianen and Wenting et al. (542), toxic properties of oxidative stresses and neuroinflammation reduce the functionality of the BBB.

The chronic levels of cocaine intake can result in dysfunctions of the BBB through cocaine induction. Roosendaal, Vianen and Wenting (546) define chronic cocaine administration to be at the levels of about 30mg/kg/day of intraperitoneal injection. Moreover, Wen, Jabbar, and Chen et al. (912) note that chronic cocaine injection can result into the rapture of the neurovascular capillaries. Experiments of the effects of cocaine administration on rats indicated that chronic cocaine administration causes ruptures of the basement membranes of the rats (Kanmogne, Primeaux and Grammas 501). The raptures caused increased permeability of the BBB that was marked by up to 50% of sodium Evans Blue or fluorescein leakage of blood into the brain of the rat just a few minutes after the administration of the cocaine molecules. Similar observations have been made in other rodents Hakobyan, Kazarian and Jabbar et al. (2062). Despite the milestone of achievements made on the effects of the drug on the BBB, much progress has not been made given the fact that most of such studies that aim at examining cocaine’s effects on the integrity of the BBB are carried out in vitro BBB models that are comprised of the brain microvascular endothelial cells in combination with the C6 astrocytes.

Hakobyan, Kazarian and Jabbar et al (2062) research on the association between cocaine administration and the permeability of the BECs indicated similar results. The experiment, like other experiments, was conducted under the same conditions and all reservations and care taken to ensure that all the necessary precautions are taken into account. The results indicated decreased electrical resistance within the transendothelial membranes and increased leakage in the FITC-Dextran across the endothelial monolayer. These effects indicated an increased permeability across the BECs just a few moments after the administration of cocaine (Yao, Duan and Buch 2544). Similar experiments have been conducted in clinical environments and resulted in similar results Hakobyan, Kazarian and Jabbar et al. (2062) involving breakdowns in BBB. Major breakdowns were witnessed in the basal ganglia accompanied by increased penetration of HIV into the CNS of the persons abusing cocaine.

Clinical studies of the functional properties of the BBB induced by cocaine revealed results that were almost attributed to the previous studies. Cocaine administration often results into the dysfunctions of the BBB. This dysfunctionality is characterized by the alterations and or loss of efficiency of the tight junction and its protein complexes. In similar researches conducted to outline the relevance of these findings, it was noticed that significant decrease in the ZO-1, as well as JAM-2, occurred in experiments with both rodents as well as the experiments carried out in vitro conditions.

The effects of cocaine administration on genetic expressions involving factors such as MMP-1 have been conducted both in vitro as well as in rodents (Acharya, Kaplan and Macdonald et al. 2487). MMP-1 handles the rearrangement of basement membrane actin aiding the formation of stress fibers that occur around the cerebral vessels. The results indicated that cocaine administration at various levels of concentration and regularity was reciprocated in the increase of gene expressions of the MMP-1 factors. Other studies such as Acharya, Kaplan and Macdonald et al. (2488) have found out that cocaine abuse leads to persistent loss of as well as the formation of changes occurring in the tight junction proteins. Besides, the presence of cocaine also leads to the reorganization of the basement membranes fibers thus leaving the brain open to allow entry of peripheral toxins. These toxins are capable of penetrating the brain fibers thus resulting in central nervous systems disorders.

Other than the various molecules discussed in the previous sections of this paper, other molecules such as the intracellular adhesion molecule 1 (commonly referred to as the ICAM-1) the vascular cell adhesion molecule 1 (VCAM) as well as the platelets endothelial cells adhesion molecules 1 (also PECAM 1) have also been investigated in relation to the effects of cocaine Acharya, Kaplan and Macdonald et al (2487) in various clinical as well as preclinical studies with cocaine-abusing humans. These molecules, as Acharya, Kaplan, and Macdonald et al. (2487) found out, bear significant effects on the functionality of the BBB. Their effects influence the functionality of the BBB. In the presence of cocaine, these molecules are affected negatively in regard to their operationalization thus leading to the dysfunction of the BBB Hakobyan, Kazarian and Jabbar et al (2063) both in vitro as well as with rodents.

To conclude, I would like to reiterate in this section that the effects of cocaine are far reaching concerning the functioning of the BBB. Hakobyan, Kazarian, and Jabbar et al, in their research on the effects and transmission of drugs into the bodies of human beings, notices that drugs delivery into the brain follows various routes. The routes of administration that leads to the abrupt injection of the drugs into the body of human beings are associated with the factors that result in drugs addiction and consequently abuse. Besides, Acharya, Kaplan and Macdonald et al. (2490) note that drugs administered over short intervals of time have greater propensities of towards severe addictive situations.

For instance, increased intake of cocaine also affects the functions of other mediators that collectively aid the functionality of the BBB. Dunn, Busch and Wyly et al. (2489) notes that the introduction of cocaine in the blood tends to alter the Blood-Brain barrier through various mediators. These mediators include the platelet driven factors responsible for growth such as PDGF. Cumulative effects of cocaine in the body further result into acute alterations in the BBB of the abusers both in the short as well as on the long-term basis.

Works Cited

Acharya, Sanket.S., et al. “Neoangiogenesis contributes to the development of hemophilic synovitis.” Blood 117.8 (2011): 2484-2493.

Dhillon, Navneet.K., et al. “Cocainemediated alterations in tight junction protein expression and modulation of CCL2/CCR2 axis across the blood brain-barrier: implications for HIV-dementia.” J Neuroimmune Pharmacol 3.1 (2008): 52-56.

Dunn, Andrea.L., et al. “Arthroscopic synovectomy for hemophilic joint disease in a pediatric population.” J Pediatr Orthop 24.4 (2004): 414-426.

Hakobyan, Zoya N., et al. “Pathobiology of hemophilic synovitis I: overexpression of mdm2 oncogene.” Blood 104.7 (2004): 2060-2064.

Kanmogne, Georgette.D., C., Ronald, Primeaux and Paula, Grammas. “HIV-1 GP120 protein alters tight junction protein expression and brain endothelial cell permeability: implication for the pathogenesis of HIV-associated dementia.” J Neuropathol Exp Neurol 64.6 (2005): 498-505.

Manco-Johnson, M.J., et al. “Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia.” NEngl J Med 357.6 (2007): 535-544.

Roosendaal, Basisarts G., et al. “Iron deposits and catabolic properties of synovial tissue from patients with haemophilia.” J Bone Joint Surg Br 80.3 (1998): 540-545.

Toborek, Michal., et al. “Mechanisms of the blood-brain-barrier disruption in HIV-1 infection.” Cell Mol Neurobiol 25.1 (2005): 181-199.

Virolle, Thierry., et al. “The Egr-1 transcription factor directly activates PTEN during irradiation induced signaling.” Nat Cell Biol 3.12 (2001): 1124-1128.

Wen, Fang.Q., et al. “c-myc protooncogene expression in hemophilic synovitis: in vitro studies of the effects of iron and ceramide.” Blood 100.3 (2002): 912-916.

Yao, Honghong, M., Luming, Duan and S-Bahnhof Buch. “Cocaine-mediated induction of platelet-derived growth factor: implication for increased vascular permeability.” Blood 117.8 (2011): 2538-2547.