How effective are neuroprotective agents?

*It is only for medical professionals to read.
Where is the dawn? At present, for the acute treatment of cerebral infarction, only intravenous thrombolysis, arterial thrombolysis, and mechanical thrombectomy are the main treatments approved by the U.
S.
Food and Drug Administration (FDA)
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Due to the limitation of the time window, only about 5%-10% of patients can actually receive recanalization treatment
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Neuroprotective agents have always been a hot topic in neurological research.
At the 24th National Conference on Neurology (NCN) of the Chinese Medical Association, Professor Hu Bo from the Department of Neurology, Union Hospital Affiliated to Huazhong University of Science and Technology discussed "Progress in Neuroprotective Agents" Done a wonderful report! 1 Intervention strategies after ischemic stroke 1.
Treatment strategies for the cerebrovascular system Reverse vascular occlusion and maintain unobstructed circulation.
Vascular recanalization (venous thrombolysis, arterial thrombolysis, mechanical thrombectomy) is currently the main treatment approved by the FDA Means
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However, as of 2020, less than 10% of patients in China have received intravenous thrombolysis or intravascular thrombectomy, and 90% of patients cannot benefit
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In addition, the antithrombotic drugs we currently use (aspirin, clopidogrel, low-molecular-weight heparin) are mainly level 2 prevention, which has limited effect in the acute phase
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2.
The goal of neuroprotection strategy: protect nerve cells from ischemia and reperfusion injury and expand the thrombolytic therapy window
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Neuroprotection research has always been a popular research in neurology.
It started early and the number of studies is huge, but the clinical application at this stage is not ideal
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2 Classification of neuroprotective agents According to different mechanisms, neuroprotective agents are divided into the following categories: 1) Ion channel modulators: such as calcium channel antagonists, N-methyl-D-aspartate (NMDA) receptor antagonists Agent 2) Antioxidants: such as free radical scavengers, 3) Anti-inflammatory drugs 4) Apoptosis inhibitors 5) Other non-drug adjuvant treatment methods 3 Neuroprotective agent research faces challenges The neuroprotective agent research dilemma, preclinical research benefits are obvious , But the clinical test result was negative
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The main problems are as follows: 1) Animal model: Early research is limited to the measurement of the final infarct size at 24 hours, and the relatively limited neurological evaluation in a short time, and does not pay attention to the long-term indicators of stroke
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No attention is paid to the influence of different genders and old age
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There are few studies on the combined application of thrombolytics
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2) Trial design: The pathological mechanism is complex and the time dimension of different targets is used to grasp the best treatment window.
The low recanalization rate reduces the efficacy of neuroprotective agents.
Different stroke types: a protective agent cannot be effective for all stroke types.
Different subgroups of pathological individuals Difference 4 The latest research progress of neuroprotective agents 1.
Human urinary kallikrein (HUK) is a glycoprotein that cleaves low-molecular-weight protein kininogen, produces effective vasodilator kinin, reduces the volume of congestion and improves neurological deficits
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Multiple mechanisms of action: inhibit TLR4/NF-KB signaling pathway, exert antioxidant and anti-inflammatory effects, increase the expression of TGF-β1, reduce neuroinflammation, inhibit glutamate-induced oxidative damage and neurotoxicity.
Clinical research results: Phase IIb and III According to the summary data of clinical trials, it is safe to start HUK within 48 hours after the onset of symptoms, and as a treatment method for acute ischemic stroke, regardless of age, gender, and complications, it has potential clinical benefits
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2.
Statins Statins reduce ischemic injury and have nothing to do with the ability to lower cholesterol, and have multiple mechanisms of action
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3.
Edaravone and borneol is a new type of neuroprotective agent made by mixing edaravone and borneol in a ratio of 4:1
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Multiple mechanisms of action: synergize with tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2 and inducible nitric oxide synthase (iNOS) and other inflammation-related proteins to relieve the brain by scavenging hydroxyl, peroxy and superoxide free radicals The results of clinical research on edema: IIb test data showed that compared with edaravone alone, it did not significantly improve the 90-day neurological function score; the IIIb test results suggested that compared with edaravone alone, edaravone dexcampanol improved the heart by 90 days.
mRs
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It has been approved by CFDA for the treatment of stroke
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TASTE trial: 48 clinical centers across the country, including 1,200 patients, the trial design is as follows: TASTE results were published on STROKE, showing that edaravone dexcamphan can effectively improve the functional prognosis of patients with acute ischemic stroke
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4.
Neuraminic acid (NA-1) is a cell-permeable peptide that interacts with the synaptic protein PSD-95 and the NR2B subunit of the NMDA receptor and the PDZ domain of neuronal nitric oxide synthase (nNOS).
Destroy its combination
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5.
Others: Vinpocetine, Natalizumab The following chart is a clinical study of neuroprotective agents in the last 5 years: At present, a variety of new neuroprotective agents have emerged, which are worthy of attention
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5 Summary Finally, Professor Hu Bo summarized the content
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The number of preclinical studies on neuroprotection is huge, but lacks consistency and clinical representativeness; a large number of neuroprotection clinical trials have failed; some effective drugs indicate the importance of pleiotropic and multi-target drugs in the treatment of stroke; new neuroprotective agents have great potential
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