Electrical microglial cell activation
US-2018193646-A1 · Jul 12, 2018 · US
US10758722B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-10758722-B2 |
| Application number | US-201815969411-A |
| Country | US |
| Kind code | B2 |
| Filing date | May 2, 2018 |
| Priority date | May 3, 2017 |
| Publication date | Sep 1, 2020 |
| Grant date | Sep 1, 2020 |
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Apparatus is provided that includes a parenchymal electrode, configured to be implanted in brain parenchyma of a subject identified as at risk of or suffering from a synucleinopathy; and a cerebrospinal fluid (CSF) electrode, configured to be implanted in a CSF-filled space of a brain of the subject, the CSF-filled space selected from the group consisting of: a ventricular system and a subarachnoid space. Control circuitry is configured to drive the parenchymal and the CSF electrodes to clear alpha-synuclein (aSyn) from the brain parenchyma into the CSF-filled space of the brain. Other embodiments are also described.
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The invention claimed is: 1. Apparatus comprising: a parenchymal electrode, configured to be implanted in brain parenchyma of a subject identified as at risk of or suffering from a synucleinopathy; a cerebrospinal fluid (CSF) electrode, configured to be implanted in a CSF-filled space of a brain of the subject, the CSF-filled space selected from the group consisting of: a ventricular system and a subarachnoid space; and control circuitry, configured to: drive the parenchymal and the CSF electrodes to clear alpha-synuclein (aSyn) from the brain parenchyma into the CSF-filled space of the brain by applying a non-excitatory current between the parenchymal and the CSF electrodes, and additionally apply deep brain stimulation using the parenchymal electrode. 2. The apparatus according to claim 1 , wherein the synucleinopathy is Parkinson's disease, and wherein the parenchymal electrode is configured to be implanted in the subject identified as at risk of or suffering from Parkinson's disease. 3. The apparatus according to claim 1 , wherein the CSF-filled space of the brain is the ventricular system, and wherein the CSF electrode is a ventricular electrode, configured to be implanted in the ventricular system. 4. The apparatus according to claim 1 , wherein the CSF-filled space of the brain is the subarachnoid space, and wherein the CSF electrode is a subarachnoid electrode, configured to be implanted in the subarachnoid space. 5. The apparatus according to claim 1 , wherein the control circuitry is configured to drive the parenchymal and the CSF electrodes to clear the aSyn by applying non-excitatory direct current between the parenchymal and the CSF electrodes. 6. The apparatus according to claim 5 , wherein the control circuitry is configured to apply the non-excitatory direct current with an average amplitude of between 0.2 and 5 mA. 7. The apparatus according to claim 5 , wherein the control circuitry is configured to apply the non-excitatory direct current with an average amplitude of less than 1.2 V. 8. The apparatus according to claim 5 , wherein the control circuitry is configured to apply the non-excitatory direct current as a series of pulses having an average pulse duration of between 0.1 ms and 300 seconds. 9. A method comprising: implanting a parenchymal electrode in brain parenchyma of a subject identified as at risk of or suffering from a synucleinopathy; implanting a cerebrospinal fluid (CSF) electrode in a CSF-filled space of a brain of the subject, the CSF-filled space selected from the group consisting of: a ventricular system and a subarachnoid space; and activating control circuitry to drive the parenchymal and the CSF electrodes to clear alpha-synuclein (aSyn) from the brain parenchyma into the CSF-filled space of the brain. 10. The method according to claim 9 , wherein the synucleinopathy is Parkinson's disease, and wherein implanting the parenchymal electrode comprises implanting the parenchymal electrode in the subject identified as at risk of or suffering from Parkinson's disease. 11. The method according to claim 9 , wherein the CSF-filled space of the brain is the ventricular system, wherein the CSF electrode is a ventricular electrode, wherein implanting the CSF electrode comprising implanting the ventricular electrode in the ventricular system, and wherein activating the control circuitry comprises activating the control circuitry to drive the parenchymal and the ventricular electrodes to clear the aSyn from the brain parenchyma into the ventricular system. 12. The method according to claim 9 , wherein the CSF-filled space of the brain is the subarachnoid space, wherein the CSF electrode is a subarachnoid electrode, wherein implanting the CSF electrode comprises implanting the subarachnoid electrode in the subarachnoid space, and wherein activating the control circuitry comprises activating the control circuitry to drive the parenchymal and the subarachnoid electrodes to clear the aSyn from the brain parenchyma into the subarachnoid space. 13. The method according to claim 9 , wherein implanting the parenchymal electrode comprises implanting the parenchymal electrode in a brainstem of the subject. 14. The method according to claim 13 , wherein implanting the parenchymal electrode comprises implanting the parenchymal electrode such that a substantia nigra of the brainstem is between the parenchymal electrode and a CSF-filled compartment of the ventricular system. 15. The method according to claim 14 , wherein implanting the CSF electrode comprises implanting the CSF electrode in the compartment of the ventricular system. 16. The method according to claim 13 , wherein implanting the parenchymal electrode comprises implanting the parenchymal electrode in a midbrain of the brainstem. 17. The method according to claim 16 , wherein implanting the parenchymal electrode comprises implanting the parenchymal electrode in a basal ganglion of the midbrain. 18. The method according to claim 17 , wherein implanting the parenchymal electrode comprises implanting the parenchymal electrode in a substantia nigra of the basal ganglion. 19. The method according to claim 9 , further comprising applying deep brain stimulation using the parenchymal electrode. 20. The method according to claim 9 , wherein activating the control circuitry to drive the parenchymal and the CSF electrodes comprises activating the control circuitry to drive the parenchymal and the CSF electrodes to clear the aSyn by applying a non-excitatory current between the parenchymal and the CSF electrodes. 21. The method according to claim 20 , wherein activating the control circuitry to drive the parenchymal and the CSF electrodes comprises activating the control circuitry to drive the parenchymal and the CSF electrodes to clear the aSyn by applying direct current between the parenchymal and the CSF electrodes. 22. The method according to claim 21 , wherein activating the control circuitry to apply the direct current comprises activating the control circuitry to apply the direct current with an average amplitude of between 0.2 and 5 mA. 23. The method according to claim 21 , wherein activating the control circuitry to apply the direct current comprises activating the control circuitry to apply the direct current with an average amplitude of less than 1.2 V. 24. The method according to claim 21 , wherein activating the control circuitry to apply the direct current comprises activating the control circuitry to apply the direct current as a series of pulses. 25. The method according to claim 24 , wherein activating the control circuitry to apply the direct current as the series of pulses comprises activating the control circuitry to apply the direct current as the series of pulses having an average pulse duration of between 0.1 ms and 300 seconds. 26. The method according to claim 9 , further comprising disposing a midplane treatment electrode in or over a superior sagittal sinus, wherein activating the control circuitry comprises activating the control circuitry to clear the aSyn from the CSF-filled space of the brain to the superior sagittal sinus, by applying a treatment current between the midplane treatment electrode and the CSF electrode. 27. The method according to claim 9 , wherein the cerebrospinal fluid (CSF) electrode is a first a cerebrospinal fluid (CSF) electrode, wherein the
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