Gender-dependent mechanisms of injury and repair

Background: Glial Maturation Factor Beta (GMFB) is a highly conserved brain-enriched protein implicated in immunoregulation, neuroplasticity and apoptosis, processes central to neural injury and repair following cerebral ischaemia. Therefore, we examined if changes in neurocellular GMFB expression and release can be used to assess brain injury following ischaemia. Methods and Results: Immunofluorescence staining, Western blotting, immunohistochemistry and ELISA were used to measure GMFB in cultured neurons and astrocytes, rat brain tissues and plasma samples from stroke model rats and stroke patients, while cell viability assays, TTC staining and micro- PET were used to assess neural cell death and infarct severity. Immunofluorescence and immunohistochemistry revealed GMFB expression mainly in astrocyte and neuronal nuclei but also in neuronal axons and dendrites. Free GMFB concentration increased progressively in the culture medium during hypoxia-hypoglycaemia treatment. Plasma GMFB concentration increased in rats subjected to middle cerebral artery occlusion (MCAO, a model of stroke-reperfusion) and in stroke patients. Plasma GMFB in MCAO model rats was strongly correlated with infarct size (R2=0.9582). Plasma GMFB concentration was also markedly elevated in stroke patients within 24 h of onset and remained elevated for more than one week. Conversely, plasma GMFB elevations were not significant in myocardial infarct patients and stroke patients without infarction. Conclusion: GMFB has the prerequisite stability, expression specificity and response dynamics to serve as a reliable indicator of ischaemic injury in animal models and stroke patients. Plasma GMFB may be a convenient non-invasive adjunct to neuroimaging for stroke diagnosis and prognosis.

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Changes in Crossed Spinal Reflexes After Peripheral Nerve Injury and Repair

Journal of Neurophysiology ◽

10.1152/jn.00305.2001 ◽

2002 ◽

Vol 87 (4) ◽

pp. 1763-1771 ◽

Cited By ~ 34

Author(s):

Antoni Valero-Cabré ◽

Xavier Navarro

Keyword(s):

Sciatic Nerve ◽

Action Potential ◽

Peripheral Nerve ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Tibialis Anterior ◽

Tibial Nerve ◽

Spinal Reflexes ◽

Injury And Repair

We investigated the changes induced in crossed extensor reflex responses after peripheral nerve injury and repair in the rat. Adults rats were submitted to non repaired sciatic nerve crush (CRH, n = 9), section repaired by either aligned epineurial suture (CS, n = 11) or silicone tube (SIL4, n = 13), and 8 mm resection repaired by tubulization (SIL8, n = 12). To assess reinnervation, the sciatic nerve was stimulated proximal to the injury site, and the evoked compound muscle action potential (M and H waves) from tibialis anterior and plantar muscles and nerve action potential (CNAP) from the tibial nerve and the 4th digital nerve were recorded at monthly intervals for 3 mo postoperation. Nociceptive reinnervation to the hindpaw was also assessed by plantar algesimetry. Crossed extensor reflexes were evoked by stimulation of the tibial nerve at the ankle and recorded from the contralateral tibialis anterior muscle. Reinnervation of the hindpaw increased progressively with time during the 3 mo after lesion. The degree of muscle and sensory target reinnervation was dependent on the severity of the injury and the nerve gap created. The crossed extensor reflex consisted of three bursts of activity (C1, C2, and C3) of gradually longer latency, lower amplitude, and higher threshold in control rats. During follow-up after sciatic nerve injury, all animals in the operated groups showed recovery of components C1 and C2 and of the reflex H wave, whereas component C3 was detected in a significantly lower proportion of animals in groups with tube repair. The maximal amplitude of components C1 and C2 recovered to values higher than preoperative values, reaching final levels between 150 and 245% at the end of the follow-up in groups CRH, CS, and SIL4. When reflex amplitude was normalized by the CNAP amplitude of the regenerated tibial nerve, components C1 (300–400%) and C2 (150–350%) showed highly increased responses, while C3 was similar to baseline levels. In conclusion, reflexes mediated by myelinated sensory afferents showed, after nerve injuries, a higher degree of facilitation than those mediated by unmyelinated fibers. These changes tended to decline toward baseline values with progressive reinnervation but still remained significant 3 mo after injury.

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CELL INJURY AND REPAIR

Clinics in Chest Medicine ◽

10.1016/s0272-5231(21)00132-5 ◽

1981 ◽

Vol 2 (3) ◽

pp. 357-375

Author(s):

EDWARD J. CAMPBELL ◽

ROBERT M. SENIOR

Keyword(s):

Cell Injury ◽

Injury And Repair

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Microglia in Neurodegenerative Events—An Initiator or a Significant Other?

International Journal of Molecular Sciences ◽

10.3390/ijms22115818 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5818

Author(s):

Gaylia Jean Harry

Keyword(s):

Neurovascular Unit ◽

Cell Types ◽

In Vitro Assays ◽

Significant Other ◽

Neurodegenerative Process ◽

Target Sites ◽

Systemic Factors ◽

Injury And Repair ◽

The Brain

A change in microglia structure, signaling, or function is commonly associated with neurodegeneration. This is evident in the patient population, animal models, and targeted in vitro assays. While there is a clear association, it is not evident that microglia serve as an initiator of neurodegeneration. Rather, the dynamics imply a close interaction between the various cell types and structures in the brain that orchestrate the injury and repair responses. Communication between microglia and neurons contributes to the physiological phenotype of microglia maintaining cells in a surveillance state and allows the cells to respond to events occurring in their environment. Interactions between microglia and astrocytes is not as well characterized, nor are interactions with other members of the neurovascular unit; however, given the influence of systemic factors on neuroinflammation and disease progression, such interactions likely represent significant contributes to any neurodegenerative process. In addition, they offer multiple target sites/processes by which environmental exposures could contribute to neurodegenerative disease. Thus, microglia at least play a role as a significant other with an equal partnership; however, claiming a role as an initiator of neurodegeneration remains somewhat controversial.

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Methods, Protocols, Guidance and Standards for Performance Evaluation for Point-of-Use Water Treatment Technologies: History, Current Status, Future Needs and Directions

Water ◽

10.3390/w13081094 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1094

Author(s):

Emily S. Bailey ◽

Nikki Beetsch ◽

Douglas A. Wait ◽

Hemali H. Oza ◽

Nirmala Ronnie ◽

...

Keyword(s):

Drinking Water ◽

Water Treatment ◽

Enteric Bacteria ◽

Current Status ◽

Household Water Treatment ◽

Produce Water ◽

Point Of Use ◽

Treatment Technologies ◽

Injury And Repair ◽

Testing Protocols

It is estimated that 780 million people do not have access to improved drinking water sources and approximately 2 billion people use fecally contaminated drinking water. Effective point-of-use water treatment systems (POU) can provide water with sufficiently reduced concentrations of pathogenic enteric microorganisms to not pose significant health risks to consumers. Household water treatment (HWT) systems utilize various technologies that physically remove and/or inactivate pathogens. A limited number of governmental and other institutional entities have developed testing protocols to evaluate the performance of POU water treatment systems. Such testing protocols are essential to documenting effective performance because inferior and ineffective POU treatment technologies are thought to be in widespread use. This critical review examines specific practices, procedures and specification of widely available POU system evaluation protocols. Testing protocols should provide standardized and detailed instructions yet be sufficiently flexible to deal with different treatment technologies, test microbe priorities and choices, testing facility capabilities and public health needs. Appropriate infectivity or culture assays should be used to quantify test enteric bacteria, viruses and protozoan parasites, or other appropriate surrogates or substitutes for them, although processes based on physical removal can be tested by methods that detect microbes as particles. Recommendations include further research of stock microbe production and handling methods to consistently yield test microbes in a realistic state of aggregation and, in the case of bacteria, appropriately physiologically stressed. Bacterial quantification methods should address the phenomenon of bacterial injury and repair in order to maximally recover those that are culturable and potentially infectious. It is only with harmonized national and international testing protocols and performance targets that independent and unbiased testing can be done to assure consumers that POU treatment technologies are able to produce water of high microbial quality and low health risk.

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Conceptual and Practical Issues in the Pharmacological Treatment of Brain Injury

Journal of Neural Transplantation and Plasticity ◽

10.1155/np.1993.227 ◽

1993 ◽

Vol 4 (3) ◽

pp. 227-237 ◽

Cited By ~ 2

Author(s):

Donald G. Stein ◽

Marylou M. Glasier ◽

Stuart W. Hoffman

Keyword(s):

Central Nervous System ◽

Brain Injury ◽

Time Course ◽

Chemical Activity ◽

Behavioral Testing ◽

Naturally Occurring ◽

New Information ◽

Definition Of ◽

Injury And Repair ◽

The Brain

It is only within the last ten years that research on treatment for central nervous system (CNS) recovery after injury has become more focused on the complexities involved in promoting recovery from brain injury when the CNS is viewed as an integrated and dynamic system. There have been major advances in research in recovery over the last decade, including new information on the mechanics and genetics of metabolism and chemical activity, the definition of excitotoxic effects and the discovery that the brain itself secretes complex proteins, peptides and hormones which are capable of directly stimulating the repair of damaged neurons or blocking some of the degenerative processes caused by the injury cascade. Many of these agents, plus other nontoxic naturally occurring substances, are being tested as treatment for brain injury. Further work is needed to determine appropriate combinations of treatments and optimum times of administration with respect to the time course of the CNS disorder. In order to understand the mechanisms that mediate traumatic brain injury and repair, there must be a merging of findings from neurochemical studies with data from intensive behavioral testing.

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