Hyponatremia and Central Pontine Myelinolysis

What is hyponatremia? Information regarding CPM and EPM.

Archive for the month “February, 2013”

Brain injury: What causes an increase in symptoms?

I have never really thought to research, why would a brain injury progress after an injury. Good news, later is better than never.

It finally hit me that I might find research documenting that after a brain injury, damage continues to occur. I truly don’t understand why these connections don’t come to me.

It irks me.

I might have discussed parts of this subject before. I have believed that the reason people like Jeffery, Michael and Deb, or even the NFL players, experience an improvement and then after a few years a decline in their health, an increase in symptoms, is because there is an immune response that causes further damage.

Some people after they have surgery, in a few years, they have further issues caused by scar tissue.

I have a history of endometriosis. I had a surgery for endometriosis, and it was less than two years later that I was experiencing significant pain. When the doctor did an exploratory surgery, he found scar tissue. He also found significant intestinal distention, but he did not know what had caused it.

Anyway, within a 12 to 18 month period, I had formed significant scar tissue because I had the surgery from endometriosis.

Scar tissue forms from the trauma that was inflicted in the first surgery.

It is in my opinion that this is what happens to those who have an improvement and then experience a decline in health, especially with cognitive issues and memory.

This post will investigate research that shows this connection after brain injury, from stroke, trauma, and other brain insults.

The following paragraph explains exactly what we experience and what might be the reason behind it. It explains that there is a recovery period where symptoms show improvements, and then as time progresses, there is an increase in symptoms:

Despite the tremendous interest in neural stem cell biology, there is little mechanistic insight into stem cell survival following common conditions induced by trauma or other brain insults. Recently, many paradigms of brain injury, including TBI, seizures, stroke, hypoxia-ischemia, and neurodegenerative diseases, implicate neural stem cells in the remodeling that occurs following such injuries (Arvidsson et al., 2002; Jin et al., 2001; Kernie et al., 2001a; Miles and Kernie, 2008; Parent et al., 2002; Parent et al., 1997; Zhang et al., 2001). The physiologic relevance of this proliferation remains unknown, but it may in part explain some of the spontaneous recovery that occurs in all of these disease states. Alternatively, aberrant neurogenesis after injury could contribute to ongoing morbidity that impairs functional recovery. In the following sections, we describe the current knowledge and outstanding research questions in the field of injury-induced neurogenesis. We first focus on experimental stroke and the SVZ, and then shift to TBI models and dentate granule cell neurogenesis.    (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864918/)

The above article is difficult for me to understand, so I will have a friend try to decipher it in greater detail and get back to me in regards to the relevance in relation to the injuries that we suffer. I believe it is stating that at this point in time, they have not been able to determine if the cells that repair damage in the course of stroke, etc are beneficial, beneficial in the beginning and then cause damage or have no direct consequence in brain injury. I really am uncertain of their direction in the article. They might point out that this is an area that needs to be investigated further. They might also be saying that these cells are only activated for a short period and then die off, and that it is this dying off period that causes the increase in symptoms. That would be an interesting thought, that I have not considered previously:

Since it is reasonably well established that hippocampal progenitors are activated by injury and result in increased numbers of new neurons within the dentate gyrus, ongoing studies can now be directed at relevance and mechanism. First, it needs to be established whether injury-induced neurogenesis is an adaptive response. There are three possibilities for its ultimate relevance. First, the generation of new neurons might be beneficial and contribute to recovery of learning and memory and possibly other functions impaired by brain injury. Second, neurogenesis may contribute to TBI-related morbidity such as temporal lobe epilepsy, which occurs relatively commonly following moderate and severe TBI. Finally, this reservoir of progenitors may be nothing more than a developmental remnant that is incapable of providing functionally relevant neurons into the sophisticated hippocampal circuitry.


The next article states that there was research as early as 2003 showing that chemotherapy could cause brain injury. They speculated that it was being caused by possible inflammation, damage to the grey matter and damage to the white matter, or that it is possible that an immunological response caused the injury.

 Although the available evidence suggests a fairly diffuse pattern of changes, memory and executive functions could be preferentially affected. Preliminary data also suggest that some individuals might be more vulnerable than others, leading to investigation of genetic and other risk factors. The greatest gap in our knowledge regarding chemotherapy-related cognitive changes is a lack of understanding of the mechanism or mechanisms that account for the observed changes. Several pathophysiological candidates include direct neurotoxic effects leading to atrophy of cerebral gray matter (GM) and/or demyelination of white matter (WM) fibers, secondary immunologic responses causing inflammatory reactions, and microvascular injury. Altered neurotransmitter levels and metabolites could constitute an additional mechanism related to neurotoxic effects. Advanced brain imaging techniques can directly or indirectly assess many of these mechanisms, but to date there has been very limited application of these tools. Morphometric magnetic resonance imaging (MRI), functional MRI (fMRI), diffusion tensor imaging (DTI), and MR spectroscopy (MRS) are noninvasive techniques that could yield important complementary data regarding the nature of neural changes after chemotherapy. Electrophysiological studies and targeted molecular imaging with positron emission tomography (PET) could also provide unique information.


It is a bit surprising that this information was available in 2003, but it took more than 8 years to get the information to the public. I don’t understand why.

Another abstract explains again, that there seems to be an initial injury and then an immune system response results in long term cognitive decline. It goes on to explain that anti-inflammatory agents might be able to prevent or treat this immune response. I’m sorry that I am unable to get full access to this article. Hopefully, at some point in the future, I will be able to include follow up information for these abstracts.

Brain damage following traumatic injury is a result of direct (immediate mechanical disruption of brain tissue, or primary injury) and indirect (secondary or delayed) mechanisms. These secondary mechanisms involve the initiation of an acute inflammatory response, including breakdown of the blood-brain barrier (BBB), edema formation and swelling, infiltration of peripheral blood cells and activation of resident immunocompetent cells, as well as the intrathecal release of numerous immune mediators such as interleukins and chemotactic factors. An overview over the inflammatory response to trauma as observed in clinical and in experimental TBI is presented in this review. The possibly harmful/beneficial sequelae of post-traumatic inflammation in the central nervous system (CNS) are discussed using three model mediators of inflammation in the brain, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and transforming growth factor-β (TGF-β). While the former two may act as important mediators for the initiation and the support of post-traumatic inflammation, thus causing additional cell death and neurologic dysfunction, they may also pave the way for reparative processes. TGF-β, on the other hand, is a potent anti-inflammatory agent, which may also have some deleterious long-term effects in the injured brain. The implications of this duality of the post-traumatic inflammatory response for the treatment of brain-injured patients using anti-inflammatory strategies are discussed.


The following articles I can’t access, but they seem to describe that this immune response is also prevalent and possible related to cognitive deficits after exposure to carbon monoxide poisoning.

This article hints that there is a cognitive impact after exposure to carbon monoxide:

Neuropsychiatric aspects of carbon monoxide poisoning: diagnosis and management Adv. Psychiatr. Treat. 2012 18 (2) 94-101

The next abstract shows that there is a neuropathophysiological impact that occurs after exposure to carbon monoxide:

The neuropathological sequelae of carbon monoxide (CO) poisoning cannot be explained by hypoxic stress alone. CO poisoning also causes adduct formation between myelin basic protein (MBP) and malonylaldehyde, a reactive product of lipid peroxidation, resulting in an immunological cascade. MBP loses its normal cationic characteristics, and antibody recognition of MBP is altered. Immunohistochemical evidence of degraded MBP occurs in brain over days, along with influx of macrophages and CD-4 lymphocytes.                              Lymphocytes from CO-poisoned rats subsequently exhibit an auto-reactive proliferative response to MBP, and there is a significant increase in the number of activated microglia in brain. Rats rendered immunologically tolerant to MBP before CO poisoning exhibit acute biochemical changes in MBP but no lymphocyte proliferative response or brain microglial activation. CO poisoning causes a decrement in learning that is not observed in immunologically tolerant rats. These results demonstrate that delayed CO-mediated neuropathology is linked to an adaptive immunological response to chemically modified MBP.


I really feel that this article, though using rats as the subjects, shows that there is the potential for continued progression of symptoms after the initial brain injury. The article suggests that brain cells continue to die up to a year after an injury in rats. If this correlates to what happens to humans, then this would potentially explain continuing cognitive issues. My opinion in this scenario is that cells that were injured, but not necessarily “killed”, continue to atrophy and die. It might be a combination of factors that cause people with brain injuries to see a progression in symptoms after seeing improvements. It is very difficult to determine without research.

Examination of the injured brains revealed substantial and progressive tissue loss with concomitant ventriculomegaly in the hemisphere ipsilateral to injury. The regions with the most notable progressive atrophy included the cortex, hippocampus, thalamus, and septum. Quantitative analysis demonstrated a significantly progressive loss of cortical tissue as well as shrinkage of the hippocampal pyramidal cell layer ipsilateral to injury over 1 year following injury. In addition, reactive astrocytosis in regions of atrophy and progressive bilateral death of neurons in the dentate hilus was observed for 1 year following injury. These results suggest that a chronically progressive degenerative process may be initiated by brain trauma. Thus, there is a temporally broad window within which to introduce novel therapeutic strategies designed to ameliorate the short and long-term consequences of brain trauma.


I have not seen a lot of information regarding the merging of these two sciences, but it would interesting to see if there has been:

Until recently, the brain was studied almost exclusively by neuroscientists and the immune system by immunologists, fuelling the notion that these systems represented two isolated entities. However, as more data suggest an important role of the immune system in regulating the progression of brain aging and neurodegenerative disease, it has become clear that the crosstalk between these systems can no longer be ignored and a new interdisciplinary approach is necessary. A central question that emerges is whether immune and inflammatory pathways become hyperactivated with age and promote degeneration or whether insufficient immune responses, which fail to cope with age-related stress, may contribute to disease. We try to explore here the consequences of gain versus loss of function with an emphasis on microglia as sensors and effectors of immune function in the brain, and we discuss the potential role of the peripheral environment in neurodegenerative diseases.


This concludes this post for now, but it does bring interesting insight and raises questions to what really does happen after a brain injury? Does the immune system cause havoc on the brain once a brain injury occurs? How long will take for those effects to be seen? Is brain tissue still dying years after the initial injury? If so, is that caused from the injury itself or from the immune response? What can we do to save what we have? Are there any precautionary measures that we can take to prevent things from degrading? Like an aspirin does with heart disease, would anti-inflammatories protect the brain?

I wish I had more answers than questions. I wish I had more definitive research, but as technology advances and the spot light on brain injuries widens, I think we will find what we can do. I think doctors will become more understanding to what we experience.

Have a great night!

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